Day :
- Advanced Nanomedicine
Location: TBA
Session Introduction
Shaoqin Sarah Gong, University of Wisconsin–Madison, USA
University of Wisconsin , USA
Title: Unimolecular Nanoparticles for Targeted Drug Delivery
Biography:
Shaoqin Sarah Gong is a Vilas Distinguished Achievement Professor in the Department of Biomedical Engineering and the Wisconsin Institute for Discovery at the University of Wisconsin–Madison. Prof. Gong’s research group has developed a series of multifunctional drug/agent nanocarriers including unimolecular micelles, polymer nanocapsules, polymer vesicles, and polymer-functionalized inorganic nanoparticles for targeted drug/agent delivery to treat and monitor various major health threats including cancers, vascular disorders, and eye diseases. She has co-authored over 140 peer-reviewed journal articles and more than 130 conference papers. Her H-index is 49. She is an editorial board member for several journals including Biomaterials, Theranostics, Biofabrication, and Nanotheranostics. She also served as an Associate Editor for Biomaterials and is the winner of a number of awards including the NSF CAREER Award and NIH Career Development Award
Abstract:
Drug nanocarriers have received increased attention because they can greatly enhance the therapeutic efficacies of drug payloads. Conventional polymer micelles, formed by the self-assembly of multiple linear block copolymers, are one of the most widely studied drug nanocarriers. However, one major concern with these conventional polymer micelles is their poor in vivo stability due to the dynamic nature of the self-assembly process. Premature rupture of these drug nanocarriers during circulation can cause a burst release of payloads into the bloodstream, which can lead to potential systemic toxicity and surrender their targeting and/or imaging abilities, thereby largely limiting their in vivo applications. Unimolecular micelles — formed by single/individual multi-arm star amphiphilic block copolymers — have been investigated to overcome this drawback. Because of their covalent nature and unique chemical structure, properly engineered unimolecular micelles can possess excellent in vivo stability (Figure 1). Moreover, due to their excellent chemical versatility, these unique unimolecular micelles can be tailored with different targeting ligands (e.g., small molecules, peptides, antibodies, nanobodies, or aptamers) and/or imaging probes (e.g., fluorophores, radioisotopes, or MRI contrast agents) to achieve multifunctionality. In particular, we have successfully developed a series of multifunctional unimolecular micelle platforms for targeted cancer (e.g., breast cancer and neuroendocrine cancer) theranostics. We have also engineered unique unimolecular micelles to treat glaucoma as well as vascular diseases (e.g., intimal hyperplasia attenuation) in a targeted manner. Moreover, other than small drug molecules, siRNA, peptides, and small proteins have also been successfully delivered via unimolecular nanoparticles through electrostatic interactions. In summary, unimolecular nanoparticles are a promising drug nanocarrier that warrants further investigation for a broader range of potential applications
Kesavan Karthikeyan
Guru Ghasidas Central University,India
Title: Chitosan Based Positively Charged Mucoadhesive Nanocarriers for Ocular Drug Delivery
Biography:
Dr. K. Kesavan is a well-versed nanotechnologist, with expertise in developing nanoparticulate systems for delivering lipophilic drugs to eye for the treatment of ocular diseases. His group developed HP-β-CD-based mucoadhesive pH induced hydrogel system and mucoadhesive microemulsion of dexamethasone for ocular delivery to treat uveitis in rabbit eye model. His research group recently studied the ion activated hydrogel system and phase transition microemulsion for ocular delivery to treat keratitis in rabbit eye model. Recently his group published a paper in ocular selfmicroemulsifying drug delivery system of prednisolone for effective treatment of uveitis in rabbit eye model. Currently, his group working on the development of the nanoparticulate drug delivery systems for ocular drug delivery, which would offer the advantages of decreased dose and dosage regimen, sustained release, improved patient compliance, and enhanced safety profile.
Abstract:
Cornea and conjunctiva carry a negative charge upon their surface, due to the presence of negatively charged mucus residues on the outer side of their membranes, and to selective active ion pumps. Ocular surface should thus be selective to positively charged delivery systems that interact with cells, leading to increased drug permeability and prolonging the pharmacological effect. Chitosan (CS), as a unique positively charged polysaccharide, has been one of the most popular biopolymers for development of drug delivery systems for various applications, due to its promising properties, including high biocompatibility, excellent biodegradability, low toxicity, as well as abundant availability and low production cost. In fact, an ionic interaction between the positively charged amino groups of CS and negatively charged sialic acid residues in mucus has been proposed as the mucoadhesion mechanism. Since last decade, increasing attention has been attracted by delivery systems fabricated from natural biopolymer-based polyelectrolyte complexes (PEC), formed by electrostatic interactions between two oppositely charged biopolymers. The preparation of nanocapsule via complex coacervation method is based on the PEC through the electrostatic interactions between cationic and anionic polymers, resulting in the formulation of insoluble spherical beads or capsules. Due to the protonation of amino groups on the backbone, CS becomes a cationic polyelectrolyte in acidic medium, which could form PEC with negatively charged polyelectrolytes, resulting in various applications. In recent years, positively charged liposomes and nanoemulsions have been used as drug carriers. CS is suitable for formulation of mucoadhesive cationic nanoemulsion because it is positively charged, making it able to adhere to the negatively charged oil globules in nanoemulsion and is soluble in diverse acids and able to interact with polyanions to form complex and nanogel. This is an effort to summarize the recent developments in the area of CS based cationic mucoadhesive nanocarriers for ocular drug delivery.
Virendra Gajbhiye
Agharkar Research Institute,INDIA
Title: Nanocarriers-mediated siRNA delivery for treatment of cancer
Biography:
Virendra Gajbhiye completed his M. Pharm and Ph.D. from Dr. H. S. Gour University, Sagar, India. He was a postdoctoral research fellow at Wisconsin Institute for Discovery, University of Wisconsin, Madison, WI, USA and Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA. Currently, he is working as a Scientist at Nanobioscience Group, Agharkar Research Institute, Pune, India. Virendra Gajbhiye has his expertise in developing multifunctional nanocarriers and their use in nanomedicine and theranostics, targeted delivery of drug/siRNA/miRNA for cancer therapy, and tissue engineering. He has extensively worked on drug targeting to brain. Currently, he is extensively working on delivery of siRNA/miRNA for treatment of breast cancer.
Abstract:
Cancer is one of the major health problems worldwide and the number of cancer cases is projected to increase by 50% by 2030. Current therapies include surgery, chemotherapy, radiation and hormonal therapy which are also used sometimes in combination to lower the risk of reoccurrence. These therapies used till date are followed by various side effects and disadvantages. Hence, newer and targeted therapies are required. One of the ways is to explore siRNA therapy that works on RNA interference mechanism. siRNA of 21-25 nucleotide long help in turning off expression of cancerous gene by directing degradation of selective mRNA. The major bottleneck in siRNA therapies is their delivery to desired cell type. siRNA does not readily cross the cellular membrane because of their negative charge and size. Moreover they are very sensitive to nuclease degradation, thus posing serious challenges in efficient delivery. Nanotechnology has been drawing a huge attention for successful and targeted delivery of siRNA. Hence we thought of using nanotechnology based vector which can be used to deliver siRNA efficiently. Multifunctional cationic dendrimers, Mesoporous silica nanoparticles (MSNPs) and other NPs are being used by use to deliver siRNA specifically to breast as well as prostate cancer cells. Our study shows that a unimolecular dendritic system (Figure 1) conjugated with luteinizing hormone releasing hormone (LHRH) analogue was able to deliver siRNA specifically to LHRH receptor overexpressing breast as well as prostate cancer cells. In one of our recent study, we observe that siRNA delivery can be achieved via unimolecular dendrimers conjugated with peptide by targeting integrin receptors of breast cancer cells. Also, cationic cobalt ferrite nanoparticles synthesized in our lab was able to successfully deliver siRNA in breast cancer cells. Similarly, our latest results show that multifunctional MSNPs (Figure 2) can be effectively use for the treatment of drug resistant breast cancer cells.
- Nanomaterials for drug delivery
Location: Radisson Hotel Narita
Session Introduction
Sung Choi
The Catholic University of Korea, Korea
Title: Nanodiamond Clusters Decorated with Folic Acid for Photothermal Tumor Therapy
Biography:
Sung-Wook Choi has an expertise in design and fabrication of functional nanoparticles for specific tumor therapy. His academic interest included fluidic device, biomaterials, scaffold, tissue engineering as well as nanomedicine. Recently, he has worked on the nanodiamonds and their applications for nanodelivery and tissue engineering. The photothermal therapy using nanodiamond was first reported in his research group.
Abstract:
Statement of the Problem: Photothermal tumor therapy (PTT) have attracted considerable attention as minimally invasive therapeutic techniques as they have a typical tissue penetration of several centimeters in biological tissues. Nanodiamonds (NDs) have a truncated octahedral composition, have emerged as promising materials due to their spherical morphology, versatile functionality, fluorescent property, colloidal stability, and high biocompatibility. Herein, we designed ND nanoclusters decorated with folic acid (FA) as a targeting moiety and utilized the photothermal effect of NDs upon NIR laser irradiation for tumor therapy.
Methodology & Theoretical Orientation: To evaluate the photothermal property of ND nanoclusters with various ND concentrations, samples were prepared and then exposed to NIR laser ( λ = 808 nm) for 5 min. in vivo tumor specificity and therapeutic efficacy also examined by injecting ND and FA-ND nanoclusters into tumor-bearing nude mice through a tail vein.
Findings: FA-ND nanoclusters exhibited specific cellular uptake to KB cells. The viability of KB cells treated with FA-ND cluster was reduced to 5.4% (94.6% of ablation ratio) along the light of NIR laser. An in vivo studies revealed that FA-ND nanoclusters selectively accumulated in tumor tissue and effectively reduced tumor volume from 36.1 ± 5.2 mm3 to 21.4 ± 4.9 mm3 by the NIR laser-exposed.
Conclusion & Significance: We demonstrated the superior performance of FA-ND nanoclusters for selective photothermal tumor therapy. We believe that FA-ND nanoclusters have great potential for selective photothermal tumor therapy.
Nana Zhao
Beijing University of Chemical Technology, China
Title: Versatile organic/inorganic nanohybrids for delivery systems
Biography:
Prof. Nana Zhao has her expertise in strategic design, controlled synthesis, and biomedical applications of organic/inorganic nanohybrids, including diagnosis of diseases, gene delivery, controlled drug-release, and imaging. Integrating the control over morphology, surface functionalization, and self-assembly strategies, the performance of nanohybrids could be improved further.
Abstract:
Organic/inorganic nanohybrids with favorable physical and chemical properties constructed form suitable surface functionalization of inorganic nanoparticles (NPs) with superior polycations are promising candidates as carriers with multi-functions. The morphology (size and shape) of NPs are considered to have an intense influence on their interaction with cells and biological systems, while the effect of morphology on gene carriers are poorly understood. We developed several facile strategies to construct organic/inorganic nanohybrids of polycations and inorganic nanoparticles. Grafting-from, grafting onto and host-guest interactions were all utilized for the fabrication of nanohybrids. Furthermore, we employed SiO2 and Au NPs as model systems to investigate the morphology effect. A series of novel gene carriers based on polycation-functionalized SiO2 and Au NPs with different morphologies were designed and synthesized, including nanospheres, nano-octahedras, nanorods, arrow-headed nanorods and chiral nanorods, et al. The morphology of both SiO2 and Au NPs is demonstrated to play an important role in gene transfection. Based on the results, star-shaped hollow silica carriers with photothermal gold caps were synthesized for the co-delivery of drugs and genes. One dimensional nanohybrids of polycations and iron oxide or quantum dots were also designed and satisfying therapeutic effects were achieved. In addition, magnetic resonance (MR) or fluorescence imaging could be realized in the same nanostructure. Therefore, combing the intriguing properties of inorganic parts, the carriers could integrate the functions of imaging and be employed for theranostic platforms. These results may provide new avenues to develop promising carriers and useful information for the application of NPs in biomedical areas.
Xiao xuan LIU
China Pharmaceutical University, P. R. China
Title: Stimulus-sensitive self-assembling amphiphilic dendrimers as siRNA delivery platform
Biography:
Xiaoxuan LIU received her Ph.D in 2010 from both Wuhan University in China and Aix-Marseille University in France. After her Ph.D, she joined the Cancer Research Center of Marseille and Interdisciplinary Center on Nanoscience of Marseille in France and performed research for five years. During this period, she got two post-doctoral grants from l’Association pour la Recherche sur les Tumeurs de la Prostate (ARTP) and l’Association Française contre les Myopathies (AFM). On 2015, she was recruited as Specially-Appointed Professors by China Pharmaceutical University in China. On 2016, she was selected by the Thousand Youth Talents Plan. Her research interest is focus on developing multi-functional dendrimers as nanovectors for nucleic acid and drug delivery, which is interdisciplinary research program including chemistry, physics, biology and medicine. Originated from these research results, she has co-authored 28 publications. Some of them have been highlighted by Nature Chemistry and reported as frontispiece or cover story.
Abstract:
RNAi with synthetic siRNA holds great promise for therapeutic applications. However, safe and successful clinical translation essentially requires further advancement of developing efficient delivery systems. Among myriad nanocarriers, amphiphilic dendrimers, marrying the characteristic of dendrimers, self-assembly performance of amphiphilic molecules and the bio-mimicry of lipids, become particularly appealing as nanovectors for drug delivery in nanomedicine, in particular for small interfering RNA (siRNA) therapeutics. Here, we reported a series of amphiphilic dendrimers are able to self-assemble into adaptive supramolecular assemblies upon interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the currently available nonviral vectors. Furthermore, a fluorinated bola-amphiphilic dendrimer was constructed for on-demand delivery of siRNA based on specific response to reactive oxygen species (ROS). The siRNA/dendrimer complexes disassemble efficiently in ROS-rich cancer cells, followed by the effective siRNA delivery and potent gene silencing. Thanks to the fluorine atoms, the ROS-responsive siRNA delivery process can be tracked through 19F-NMR analysis. Our study demonstrates that the self-assembling amphiphilic dendrimers represent novel and versatile means for functional siRNA delivery, heralding a new age of dendrimer-based self-assembled drug delivery in biomedical applications.
Arvydas Tamulis
Vilnius University Institute of Theoretical Physics and Astronomy,Lithuania.
Title: Quantum Entanglement Communications in Photoactive Synthetic Bio-Systems and in Neural Networks
Biography:
Abstract:
Julien Bras
University Grenoble Alpes,France
Title: Nanocellulose alginate composite for 3D cell growth
Biography:
Dr Julien Bras (H index: 32; 122 scientific papers, 11 patents) is Associate professor at Grenoble Institute of Technology (Grenoble INP Pagora). He is member of Institut Universitaire de France (IUF, 2016-2021). He is deputy director of LGP2 (Laboratory of Pulp & Paper Science) and head of the “Multiscale Biobased Material” group (ab. 40 pers.). He has directly supervised 23 PhD and 14 Post-doc focusing on research on Biomaterials, Nanocellulose & Specialty papers. After engineer diploma in Chemistry and a PhD on Renewable Materials in 2004, he worked in industry few years as Innovation Manager within Ahlstrom Specialty paper and then left industry to become associate professor since 2006.
Through his different experiences, he develops several competences. His expertise deals particularly with Nanocellulose, biobased and smart materials. More precisely, he proposed new way of production, characterization and functionalization of nanocellulose for several applications since more than 10 years. He has already coordinated or supervised several industrial and European projects in FP6, FP7 and Marie-Curie calls. He is involved in a Labex & Carnot institute organization as WP leader and is associate editor for an Elsevier Journal (Industrial Crops and products).
Abstract:
Dr Julien Bras (H index: 32; 122 scientific papers, 11 patents) is Associate professor at Grenoble Institute of Technology (Grenoble INP Pagora). He is member of Institut Universitaire de France (IUF, 2016-2021). He is deputy director of LGP2 (Laboratory of Pulp & Paper Science) and head of the “Multiscale Biobased Material” group (ab. 40 pers.). He has directly supervised 23 PhD and 14 Post-doc focusing on research on Biomaterials, Nanocellulose & Specialty papers. After engineer diploma in Chemistry and a PhD on Renewable Materials in 2004, he worked in industry few years as Innovation Manager within Ahlstrom Specialty paper and then left industry to become associate professor since 2006.
Through his different experiences, he develops several competences. His expertise deals particularly with Nanocellulose, biobased and smart materials. More precisely, he proposed new way of production, characterization and functionalization of nanocellulose for several applications since more than 10 years. He has already coordinated or supervised several industrial and European projects in FP6, FP7 and Marie-Curie calls. He is involved in a Labex & Carnot institute organization as WP leader and is associate editor for an Elsevier Journal (Industrial Crops and products).
Zi Sophia Gu
University of New South Wales,Australia
Title: Engineered clay nanoparticles for cancer treatment and diagnosis
Biography:
Dr Zi Sophia Gu is a Lecturer and National Health and Medical Research Council (NHMRC) Early Career Fellow in the School of Chemical Engineering at University of New South Wales (UNSW), Sydney. She obtained PhD from Australian Institute for Bioengineering and Nanotechnology at The University of Queensland (UQ), Australia, in 2011, and she was awarded a NHMRC EC Fellowship in 2013 when she started her independent research at UQ prior to joining UNSW in 2016. Sophia has been working in multidisciplinary research areas that combine the knowledge and skills across nanotechnology and biomedicine, and has developed a targeted anti-restenotic therapy and built inorganic nanoparticle platforms for diagnosing and treating diseases. She published in high-impact journals including Advanced Materials, Biomaterials, Chemistry of Materials, Materials Horizons, and Journal of Controlled Release etc. Her recent awards include The Monash Engineering Women’s Leadership Award and Deputy Vice-Chancellor (Academic) Award. Her research group focuses on developing multifunctional nanomaterials for theranostic application (disease therapy and diagnosis).
Abstract:
Recent progress in material chemistry has enabled scientists to combine therapeutic and diagnostic agents on a single nanoplatform, which is designated as theranostics [1]. However, it remains a challenge to achieve theranostics with safety and high performance. We utilised a clay nanosheet LDH as the carrier of Mn(II) and anti-cancer drug 5-FU, and synthesised a new nanocomposite with outstanding pH-ultrasensitive T1-MRI performance and enhanced drug delivery efficiency [2,3] (Figure 1). Mn(II) element was doped in LDH nanostructure by isomorphic substitution to synthesis Mn-LDH nanosheets. The generated Mn-LDH (~50nm) showed an ultrahigh T1-weighted relaxivity of 9.48 mM-1s-1 at pH 5, possibly caused by the unique microstructure of Mn ions in Mn-LDHs. The relaxivity of Mn-LDH was highly sensitive to pH, which increased sixfold when pH was reduced from 7.4 to 7.0. The Mn-LDH was effectively internalised in HT29 cells, and the anti-cancer efficiency of 5-FU was enhanced by LDH delivery (IC50=1.54 µg/ml). The in vivo MRI evaluation showed an accumulation of Mn-LDH in tumour compared with liver and kidney, and the MRI signal maintained in tumour for 72 h. The second part of this talk will present a MnLDH@SPION nanocomposite as a pH-sensitive T1/T2 dual modal MRI contrast agent, hyperthermia agent and efficient drug carrier. The nanocomposite showed T1-weighted relaxivity increased from 1.88 to 6.23 mM-1s-1 and T2-weighted relaxivity from 226.18 to 367.25 mM-1s-1. This pH-sensitive and high relaxivity is not found in SPION as T2-MRI contrast agent. The MnLDH@SPION nanocomposite also has mild hyperthermia and efficient drug delivery properties.
Dr. Asahi Tomitaka
Florida International University, Florida
Title: Development and characterization of magneto-plasmonic nanocarriers for image-guided drug delivery
Biography:
Dr. Tomitaka received Ph.D. in Electrical and Computer Engineering from Yokohama National University, Yokohama, Japan in 2011. She was a Japan Society for the Promotion of Science (JSPS) postdoctoral fellow at Kyoto University, Japan from 2011 to 2012, and a JSPS Postdoctoral Fellow for Research Abroad at University of Washington, USA from 2012 to 2014. She is currently a Postdoctoral Associate in the Department of Immunology, Florida International University (FIU). Her expertise is magnetic engineering and nanotechnology for biomedical applications
Abstract:
Drug delivery systems have shown promising results for various diseases owing to the development in nanotechnology. However, the therapeutic effect is still limited due to the lack of monitoring system after drug administration. Image-guided drug delivery is an emerging strategy which has a great potential to improve the therapeutic efficacy of drug delivery systems by adding an image guidance. The addition of imaging enables monitoring of drug distribution after administration and quantification of the drugs at target site. Among various nanoparticles developed for biomedical applications, magnetic nanoparticles have shown promise for brain targeting and magnetic resonance imaging (MRI) due to their unique magnetic properties. Gold nanoparticles possess excellent properties for various imaging modalities including X-ray computed tomography (CT) and photoacoustic imaging. Combining magnetic and plasmonic features in a single nano-structure gives multi-functionality which is suitable for image-guided drug delivery.
In this study, we synthesized magneto-plasmonic nanocarriers by a two-step process. First, magnetic nanoparticles (MNPs) were synthesized by co-precipitation, followed by gold coating of MNPs by citrate reduction. The spherical magneto-plasmonic nanoparticles with the surface plasmon resonance (SPR) peak in the visible range were synthesized in this step. In the second step, the morphology of the nanoparticles was modified to star shape to adjust SPR within the near infrared (NIR) range. This NIR responsiveness is suitable for optical imaging systems due to the long penetration of NIR light inside body. A transmission electron microscopy (TEM) study showed successful synthesis of star shaped nanoparticles. We conducted magnetic and optical characterization of the magneto-plasmonic nanocarriers, and confirmed superparamagnetic property and SPR peak within NIR region. These results indicate the capacity of magneto-plasmonic nanocarriers for drug delivery systems with highly precise image guidance using multiple imaging modalities.
- Synthesis of Nanoparticles for Drug Delivery
Location: Radisson Hotel Narita
Session Introduction
Shubiao Zhang
Dalian Minzu University ,China
Title: Cationic lipids for gene delivery in vitro and in vivo
Biography:
Dr. Shubiao Zhang now is a distinguished professor at Dalian Minzu University and a doctor supervisor at Dalian Institute of Chemical Physics and Dalian University of Technology. He is involved in the study about non-viral vectors for gene delivery and bio-active materials. He got many awards at the university including Young Backbone Teacher of Liaoning Province, New Century Excellent Talents of Ministry of Education, Academic Paper Award of Liaoning Province and Scientific and Technological Paper Award of Dalian City. He leads many research programmes supported by Natural Science Foundation of China, Ministry of Education, Hoffmann La-Roche Ltd. and some domestic companies. He published over 80 peer-reviewed articles, among them over 40 were indexed by SCI, 15 by EI with a total cites of over 1200 times. He is a reviewer for many high quality peer-reviewed journals such as Journal of Controlled Release, Bioconjucate Chemistry, Molecular Pharmaceutics and Interational Journal of Pharmaceutics.
Abstract:
Several novel tri-peptide cationic lipids were designed and synthesized for delivering DNA and siRNA. They have tri-lysine and tri-ornithine as headgroups, carbamate group as linker and 12 and 14 carbon atom alkyl groups as tails. These tri-peptide cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. Their particle size, Zeta potential and DNA-binding were characterized to show that they were suitable for gene transfection. The further results indicate that these lipids can transfer DNA and siRNA very efficiently into NCI-H460 and Hep-2 tumor cells. The selected lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for silencing distinct oncogenic pathways in lung tumors of mice, with little in vitro and in vivo toxicity
Biography:
Sakthivel Lakshmana Prabu has his expertise in Herbal formulations, nanoparticulate drug delivery system and its therapeutical applications. He is Having 17 years of professional experience with good reputed pharmaceutical industrial expertise in quality assurance, validation and formulation development. He filled 3 international patents, published 93 research articles in International and National journals. Contributed 12 book chapters and edited 2 books. Book chapter entitled “Extraction of Drug from the Biological Matrix: A Review” has been downloaded 22,000 times worldwide. As a Principal Investigator, he received a project grant from Department of Biotechnology, India for the worth of 67 Lakhs. He is serving as reviewers for eight reputed journals and an editorial board member for five journals
Abstract:
Almost 80% of the adolescent populations of the world are affected with Acne vulgaris specifically during their puberty stage of life. Bacteria develop antibiotic resistance on repeated treatment with particular antibiotics by forming a rapport between the bacteria and antibiotic. In olden days, plants were used as a medicine for several diseases. Development of formulation for the treatment of acne is a major focused research in pharmaceutical sciences especially, in cosmetic care industries. The objective of our research is to prepare silver nanoparticles from the leaf extract of Ocimum Gratissimum and develop topical herbal gel formulation for the effective treatment of acne. Based on the research literatures, the medicinal plant Ocimum gratissimum is selected due to enormous pharmacological activity in relevance to acne. Methanolic leaf extract was prepared and analyzed for its phytoconstituents. The results of the study revealed the presence of phytoconstituents like alkaloids, flavonoids, tannins and saponins in the extract. 1mM aqueous solution of silver nitrate was used with the methanolic extract of Ocimum gratissimum for the preparation of silver nanoparticles. Formation of silver nanoparticles was confirmed by UV spectroscopy. Synthesized silver nanoparticles were spherical in shape with average particle size of 207.6 nm and the polydispersity index was found to be 0.256. These synthesized silver nanoparticles were incorporated into the gel base using Carbopol 934 and HPMC (1%w/v) and evaluated for its physicochemical properties and antibacterial activity. The results demonstrated that the developed topical herbal gel had easy washability, good spreadability and pH was found to be 6.72 and 6.80. Antibacterial study of the developed formulation showed higher inhibitory activity against Propionibacterium acne, Staphylococcus aureus and Escherichia coli when compared to the extract. The results of our study concluded that silver nanoparticle of Ocimum gratissiumum in aqueous gel base may be used for the treatment of acne vulgaris.
- Smart Drug Delivery Technology
Location: Radisson Hotel Narita
Session Introduction
Ajeet Kaushik
Florida International University, USA
Title: Non-invasive delivery of magnetic drug-nano-carrier to the brain
Biography:
Ajeet Kumar Kaushik, Ph.D. (http://akaushik3.wixsite.com/nanocare), is an Assistant professor at the Centre of Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Department of Immunology of Florida International University, USA. He is recipient of various reputed awards and exploring smart electrochemical sensing systems for rapid diagnostics and nanocarriers for on-demand site-specific delivery/release of therapeutics to prevent CNS diseases. His main research interest is developing nanomedicine along with exploring novel methods of brain delivery and wearable sensors for personalized health care. Dr. Kaushik received his Ph.D. (Chemistry and Biosensors) in collaboration with the National Physical Laboratory and Jamia Milia Islamia, New Delhi, India.
Abstract:
Advancements in nano-bio-technology revolutionized health care management via investigating nanomedicine and delivery for targeted diseases. Due to easy tunable performance features these systems serves in a controlled manner and significantly useful for personalized health care. Keeping this in view, magnetically-guided brain delivery of magneto-electro nanoparticles (MENPs ± 25 nm), a drug nano-carriers capable to exhibit a. c. magnetic field stimuli responsive on-demand drug release, in C57Bl/J mice has been demonstrated. Our findings confirm uniform distribution of MENPs in the brain of mice without causing clinical toxicity and altering neurologic behavior. However, the translation of this brain delivery method for humans is not yet developed due to a mismatch of available static magnet dimension in relation to the human brain size and shape. Aiming to develop personalized nanomedicine to eradicate neuro-HIV/AIDS, we demonstrated magnetically-guided brain delivery of MENPs to the brain of an adult female baboon (Papio hamadryas) using magnetic resonance imaging (MRI) as a navigation tool. An optimized dose of MENP (22 mg/13 kg) suspended in 100 mL PBS was injected into the baboon vasculature via the saphenous vein with a flow rate of 220 mL/hr. After injection, the baboon was placed under static MRI magnetic exposure for 3 hours to achieve magnetically-guided brain delivery. MRI image analysis confirmed MENPs distribution within the brain regions such as basal ganglia, hemisphere, and vertex. The results of histopathology and blood toxicity profile studies confirmed that injected MENPs did not cause any toxicity or metabolic abnormalities. We propose utilizing MRI as a potential navigation tool for the brain delivery of magnetic therapeutic formulations to treat brain diseases for personalized health care.
- Personalized Nanomedicine
Location: Radisson Hotel Narita
Session Introduction
Dr.Ling Peng
French National Scientific Research Center (CNRS),France
Title: Charm of dendrimer nanotechnology for biomedical applications
Biography:
Dr Ling Peng is a leading expert in developing functional dendrimer nanosystems for drug delivery in biomedical applications. She has successfully established bio-inspired structurally flexible and self-assembling dendrimer nanosystems for drug and nucleic acid delivery. One of the dendrimers developed by her team has been scheduled in clinical trials. Dr Peng has coordinated and participated in different European projects and actively involved in several European CAOST Actions. She is currently a research director at the French National Scientific Research Center (CNRS), and a principle investigator at the Centre Interdisciplinaire de Nanoscience de Marseille (CINaM). Her research team has been labelled by La Ligue contre Le Cancer in France for the period of 2016-2020, and she was awarded for the Prize of Dr and Mrs Henri Labbé by the French Academy of Sciences in 2017.
Abstract:
Nanotechnology is widely expected to bring breakthroughs in specific delivery of the right therapeutic agent to the right patient at the right disease lesion. Dendrimers are ideal nanocarriers for drug delivery by virtue of their uniquely well-defined structures and multivalent cooperativity confined within a nanosized volume per se. We have established bioinspired structurally flexible and self-assembling supramolecular dendrimers for drug delivery.1-6 These dendrimers are excellent nanocarriers for personalized medicine: they are able to form modular, responsive and adaptive nanosystems, and effectively deliver various chemo- and bio-therapeutics as well as imaging agents for precise diagnosis and personalized treatment in various disease’s models. These studies have offered new perspectives in dendrimer nanotechnology based biomedical applications.
Rawan Alkahtani
Princess Nourah bint Abdulrahman University:Saudi Arabia
Title: The Implications And Applications Of Nanotechnology In Dentistry
Time : TBA
Biography:
Dr. Rawan AlKahtani is a lecturer in the Restorative Dentistry Department at Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. She graduated from King Saud University with a bachelor in Dental Science, followed by a Masters degree in Clinical Restorative Dentistry from Newcastle university, UK. She additionally obtained a certificate in nanotechnology from University of Oxford and a certificate in clinical research from Harvard University. She is currently a PhD researcher in the institute of cellular medicine, School of Dental Sciences, Newcastle University, UK.
Abstract:
The Emerging Science Of Nanotechnology, Especially Within The Dental And Medical Fields, Has Sparked Research Interest In Regards To The Level Of Improvement These Quantum Particles Can Achieve In Comparison To Conventional Materials Used. Understanding The Science Behind Quantum Technology Is Essential To Appreciating How These Materials Can Be Utilised In Our Daily Practice. The Present Paper Will Help The Reader Understand The Technology Itself Through Acknowledging Its Benefits And Limitations And Reviewing The Science Behind It And The Ethical, Social, Health, And Environmental Implications Of Nanotechnology. Additionally, Applications Of Nanotechnology In Dental Diagnostics, Dental Prevention, And Dental Materials Will Be Discussed, Including A Variety Of Commercially Available Products And Supporting Evidence.
Jyh-Ping Chen
Chang Gung University, Taiwan, ROC
Title: Thermosensitive Magnetoliposome Nanodrugs for Cancer Therapy
Biography:
Dr. Jyh-Ping Chen has been a professor in Chemical and Materials Engineering at Chang Gung University since 1997. He is currently a researcher in Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital and holds joint appointments as Professor in Department of Materials Engineering, Ming Chi University of Technology, and Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taiwan, ROC. He received his BS degree in Chemical Engineering from National Taiwan University in 1981 and PhD in Chemical Engineering from Pennsylvania State University in 1988. Professor Chen has published over 150 papers in SCI journals with more than 3500 citations. He is a guest editor or editorial board member for 13 international journals and a peer reviewer for more than 50 reputed SCI journals. His current research interests include biomaterials, tissue engineering and drug delivery.
Abstract:
Dr. Jyh-Ping Chen has been a professor in Chemical and Materials Engineering at Chang Gung University since 1997. He is currently a researcher in Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital and holds joint appointments as Professor in Department of Materials Engineering, Ming Chi University of Technology, and Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taiwan, ROC. He received his BS degree in Chemical Engineering from National Taiwan University in 1981 and PhD in Chemical Engineering from Pennsylvania State University in 1988. Professor Chen has published over 150 papers in SCI journals with more than 3500 citations. He is a guest editor or editorial board member for 13 international journals and a peer reviewer for more than 50 reputed SCI journals. His current research interests include biomaterials, tissue engineering and drug delivery.Furthermore, in vitro cell culture experiments confirmed that the drug carriers exhibited no cytotoxicity against fibroblasts and cancer cells. The drug-loaded carriers also showed better therapeutic effect toward killing cancer cells compared with free drugs. The blood hemolysis assay showed non-hemolytic activity, indicating good blood compatibility. Finally, in vivo experiments using xenograft tumor mouse model with U87 human glioblastoma cells with magnetic guidance and AMF treatment demonstrated the efficacy and safety of treatment using TCML-CPT11-shRNA.
- Nano Pharmaceuticals
Location: Radisson Hotel Narita
Session Introduction
Dr.Akhtar Aman
Shaheed Benazir Bhutto University, Pakistan
Title: Modified Glycol Chitosan Nanocarriers Carry Hydrophobic Materials into Tumours
Biography:
Dr.Akhtar Aman has completed his PhD at the age of 30 years from Peshawar University under Hec Scholarship. During his Ph.D studies, Dr.Akhtar also worked as visiting Scientist at Center for Cancer Medicine,School of Pharmacy, University college London,UK. He is currently serving as Assistant Professor of Pharmaceutics at Shaheed Benazir Bhutto University,Sheringal Pakistran. He has published more than 10 papers in reputed journals.
Abstract:
Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study is to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosanweresynthesized by chemical grafting of palmitic acid N-hydroxysuccinimideand quaternisationto glycol chitosan backbone.To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymerhad the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001)Using the hydrophobic fluorescent dyeNile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenografttumorin-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reducedside effects associated with current available formulations but alsoincreasedtheir transport through the biological barriers, thus making it a good delivery system.
- Drug Delivery Research
Location: Radisson Hotel Narita
Session Introduction
Lilach Agemy
Weizmann Institute of Science, Israel
Title: Tumor Microenvironment-Targeted Bacteriochlorophylls as Theranostic Agents for Triple Negative Breast Cancer
Biography:
Dr. Lilach Agemy has her expertise in vascular biology and tumor/ atherosclerosis microenvironment. Developed highly specific delivery of different probes and drugs for cancer/ atherosclerosis therapy with hands on experience in the synthesis, modification, and characterization of different nanoparticles systems including magnetic iron based nanoparticles. Her current research focuses on using new targeted derivatives for photodynamic therapy with bacteriochlorophyll that were developed in our lab and based on TOOKAD, which was recently approved by EMA. Dr. Agemy is working in an extensively multidisciplinary environment involving Biologists, Chemists, Physicists and Bioengineers with participation ranging from designing, performing experiments, analyzing imaging and other biological data, and is involved in training graduate students and postdocs.
Abstract:
Cytotoxic drugs that target specific receptors on cancer cells and supporting vasculature often fail to convey significant therapeutic benefit, despite their extensive tumor uptake and high toxicity in cell cultures. A recent example is provided by Cilengitide®, a cyclic Arg-Gly-Asp (cRGD) that accumulate in tumors but fails to delay cancer progression. In this study we rationalized the current failure of cRGD based clinical trials by assessing the tumor heterogeneity, showing that significant populations of cancer and endothelial cells do not accumulate the cRGD agents. We further tested the hypothesis that bystander cell death propagation initiated by agents coupled to cRGD molecules can effectively eradicate the entire tumor even if taken by the limited cell populations. The new approach was applied to mice grafted with metastatic 4T1 tumors in their mammary pad. This model is considered good representative for triple negative breast cancer (TNBC), a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents with high rate of treatment failure and mortality.
Results: Using STL-6014, a cRGD tagged with a fluorescing and photoactive bacteriochlorophyll derivative (Bchl-D), we showed that STL-6014 can specifically and noninvasively target orthotopic TNBC tumors as well as lung metastatic tumor lesions trough integrin receptors expressed on different cell populations. The apparent high tumor uptake reflects the integrin expression by these cells. High cRGD uptake confers death of cancer and stroma cells while cells lacking integrin expression remains alive and drive tumor proliferation. This therapeutic obstacle is solved by self-promoting death signal initiated by photo-activation of the Bchl-D tags in the β3 expressing cells. Rapid propagation of cell apoptosis/necrosis via bystander effect results 62% primary tumor ablation in mice bearing 4T1.
Conceptual significance: The study provides rationale and new means for paradigm shift in cell-targeted therapies, understanding and overcoming failures of therapies that target specific cell populations in the tumor microenvironment.
Sonal Thakore
The Maharaja Sayajirao University of Baroda,India
Title: Polymers for Stimuli Responsive Drug Delivery Applications: Structural Manipulation for Mimicking Solitary, Dual and Multiple Responses
Biography:
Sonal Thakore has completed her PhD at the age of 27 years from The Maharaja Sayajirao University, Baroda, Gujarat, India. She is assistant professor at The Maharaja Sayajirao University, Baroda, Gujarat, India and has 12 years of teaching experience. She has guided for 4 students for Ph.D. and published over 40 publications in reputed international journals. She has been granted Indian Patent No. 274199 dated 19/8/2010, “A process for synthesis of nanosized hydrophobic polysaccharide derivatives.” She has presented papers at several national and international conferences, served as reviewer for reputed international journals.
Abstract:
The design of stimuli responsive polymers is an emerging area in the field of medicine and biology, which makes use of practical and effective approach for treatment and eradication of several diseases. Based on the response triggered by conformational and structural modifications of polymers, they can be utilized for stimuli responsive applications. In order to elucidate the recent advances in the field the research carried out in the last decade is summarized. A summary of the variety of stimuli such as pH, temperature, enzyme, light etc. along with the relevant polymers used for their response thorough the corresponding triggering mechanisms will be presented. The future challenges and barriers for development of smart polymers will also be discussed.
Saeedeh Ghiasvand
Malayer University,Iran
Title: Bacteriophage: the smallest organisms with Remarkable abilites
Biography:
Dr. Saeedeh Ghiasvand has completed her Ph.D. in molecular Genetic at the age of 27 years from Tarbiat Modares University. she is the assistant professor in biology department in Malayer University. she special areas of interest are phage display technology and targeted therapy
Abstract:
The discovery of ligands that selectively bind to a certain target plays a vital role in the generation of clinically relevant diagnostics and therapeutics. Phage display as a powerful methodology has proven very promising in the identification of many target specific ligands. But there is another aspect that phage can act as biomarkers. Phage colonized in the people bodies from the earliest moments of life and become our fellow travelers through the life. Phageome seems to be unique to each individual and alter in each different situations. phagosome structure and composition change depend on the physiological or pathological status of the body. Phageome oriented studies are vital to advance our understanding of the potential roles of phages in clinical application. The identification of phagosome as health or disease biomarker provides novel opportunities for unraveling the mechanisms underlying different diseases, stratifying patients, and developing more effective diagnostic and therapeutic approaches. Recent finding favor the suggestion that the phage might directly (phagosome that colonized in our body) or indirectly ( phage display technology) act as potential biomarkers for diagnosis and treatment.
Rayan Sabra
University of Nottingham, Malaysia
Title: A novel approach toward mucoadhesive and tumour targeting curcumin nanoparticles for colon cancer treatment.
Biography:
Abstract:
Colon cancer is a crucial health problem worldwide. The current interventions combining surgery and chemotherapy have only partially addressed the issue of ineffectiveness and recurrence in patients [1]. Traditionally most anticancer drugs are administered intravenously even for remote cases as in colon cancer, where residential presence of the anticancer drug at the colon is an obvious desirability. Thus, encapsulating drug loaded oral formulations that offer cancer-targeting capability are a promising alternative to improving treatment of colon cancer, whereby localised drug concentration is increased and side effects are minimised [2]. Nanoparticles offer a rational choice due to its large surface area to volume ratio, but should withstand the milieu of the upper gut and deliver its cargo at the colon. In this view, we have developed a modified pectin-chitosancurcumin nanoparticle system (MCPCNPs) (Figure 1) for targeted delivery of curcumin to the colon. The MCPCNPs presented high mucoadhesion propensity in simulated colonic media and minimal at pH 1.2 (stomach). We further enhanced the MCPCNPs by coupling contamumab antibody that target the death receptor (DR5) present on the tumour surface, through a two-step carbodiimide (EDC) approach. The in vitro evaluation of the conjugation was examined using some available analytical techniques, while the conjugation efficiency was confirmed via the micro-bicinchoninic acid assay. The in vitro cytotoxicity and cellular apoptosis assays of the composite nanoparticle-antibody-curcumin-delivery system are being studied currently. In general, the data obtained so far strongly suggests that the formulated mucoadhesive, targeted curcumin-loaded nanoparticles have the potential to be applied as an orally deliverable colon cancer treatment
- Design of Nanodrugs
Location: Radisson Hotel Narita
Session Introduction
Rohidas Arote
Seoul National University, Republic of Korea
Title: Design of Multifunctional Polymeric Carriers for Cancer Gene Therapy
Biography:
Prof. Arote Rohidas is an Associate Professor and the director of Nanomedicine Laboratory in the Dept. of Molecular Genetics, School of Dentistry, Seoul National University. Prof. Arote is one of the leading scientists in the field of biomaterials development for gene delivery especially for cancer treatment. His research on DNA therapeutics, biodegradable polymeric carriers, and nanoparticles has been published in over 50 international journals and also produced various patents. Prof. Arote’s lab is focusing on development of novel biomaterials and nanotechnologies for a variety of medical applications including gene/drug delivery, diagnosis, bioimaging, and regenerative medicine also on both fundamental and applied questions in the cross-disciplinary fields of biomaterials and medicine in order to develop novel therapeutic methods for the treatment of cancer, obesity, and cardiovascular disease.
Abstract:
Primary Objectives Of Gene Therapy Are To Correct The Genetic Defects That Underlie A Disease Process And To Provide Supplemental Therapeutic Modality Through Genetic Engineering. Over 75% Of Current Gene Therapy Is Performed Using Viruses As Gene Delivery Vehicles. However, With Viruses, There Are Serious Concerns Over The Issues Of Toxicity, Immunogenicity, Payload Gene Size Limitations, And Difficulty In Scale Up For Industrial Production. Non-Viral Vectors Therefore Have Attracted Attention From Academic And Industrial Point Of View. Among The Non-Viral Vectors, Polymeric Systems Offer Several Important Advantages. First, Polymers Are Tremendously Versatile And Can Provide Physical, Chemical, And Biological Properties That Are Necessary For Gene Delivery Applications. Second, Polymers Can Be Synthesized In Parallel Synthesis Pathways For High-Throughput Screening Of Biocompatibility And Transfection Efficiency. Third, Various Formulations, Designs, And Geometrics Can Be Made From Polymeric Materials For Specific Types Of Gene Delivery Applications. Moreover, The Surface Chemistry Of Polymers Can Be Easily Modified With Biological Ligands For Site Specific Targeting In The Body. However, Some Non-Degradable Polymers Accumulate In The Body Resulting In The Cytotoxicity And Thus The Reduction In Their Gene Transfer Ability. Even Though, Low Molecular Weight Polymers, Which Can Be Eliminated Via Kidney Is An Alternative Choice, Exhibits Lower Colloidal Stability And DNA Condensation Due To Their Reduced Number Of Electrostatic Interactions Thus Reduced Transfection Efficiency.
As Biodegradable Polymers Are Designed To Contain A Combination Of Various Functional Components, It Is Likely That Engineered Systems For Non-Viral Gene Delivery, Especially With The Application Of Biodegradable Ester Linkage Will Eventually Be Constructed. This Biodegradable Linkage Approach To Vector Development Is Giving Way To A Safety Profile Where Low Molecular Weight Polyethylenimines Are Coupled With Diacrylates And Sugar Alcohol Linkers To Yield High Molecular Weight Poly(Ester Amine)S (Peas) With Reduced Cytotoxicity And High Transfection Efficiency. The Need For A Safety And Biocompatibility Approach Extends To In Vitro Investigations, As Modifications Intended For In Vivo Applicability Can Significantly Affect Both In Vitro And In Vivo Performance.
- Young Research Forum
Location: Radisson Hotel Narita
Session Introduction
Pattravee Niamprem
Naresuan University, Thailand
Title: Surface Activity Of Nanostructured Lipid Carriers (Nlcs) On Meibomian Lipid Films
Biography:
Pattravee Niamprem is a Ph.D. student in the Pharmaceutical Sciences at Naresuan University, Thailand. She studied her undergraduate degree of Cosmetic Science, and completed her master’s degree of Pharmacology and biomolecular Sciences in the title of “Development and characterization of lutein loaded SNEDDS for enhanced absorption Caco-2 cell” from Naresuan University also. Her main research interests are nanoparticles drug delivery, drug delivery systems, ocular drug delivery system, and pharmaceutical development. For her doctoral thesis, she is developing a new ophthalmic formulation for dry eye disease.
Abstract:
Blinking spreads a protective tear film over the exposed ocular surface. Defects in a lipid layer (TFLL) at its air interface can cause tear film instability: a major cause of dry eye. Some eye drops target repair of the TFLL, but are transient. To obtain a more sustained effect, NLCs have been developed to slowly release their lipid contents. The interactions of differently formulated NLCs with films made from meibum (the major component of the TFLL) have been investigated. NLC formulations were injected into the aqueous subphase of a Langmuir trough and their surface activity or ability to alter surface pressure-area profiles of Meibomian lipid films was tested. Fluorescent markers and electron microscopy were also used to determine structural changes to the films due to adsorption of NLCs. Gelucire 43/01 and cetyl palmitate NLCs (40nm), or glyceryl behenate NLCs (300nm) were used. The 40nm NLCs had greater surface activity (higher Πmax) than the 300nm NLCs. The nature of both the surfactant and the solid lipids used in the formulation affected the surface activity of NLCs. Fluorescence microscopy showed that the NLCs adsorbed to the Meibomian lipid films and were homogeneously spread throughout the film. This was confirmed with SEM. In conclusion NLCs processes strongly surface active and can integrate with meibomian lipid films. The type of interaction can be tailored by altering the surfactant and solid lipids used in the formulation of the NLCs which provides flexibility to develop efficient formulations for specific dry eye conditions.
Nayab Tahir
University of Helsinki, Finland
Title: Merging the Two Worlds: Lipid-polymer Hybrid Nanoparticles for the Controlled Drug Delivery of Chemotherapeutic Agents
Biography:
Nayab Tahir received Pharm-D and M.Phil. (Pharmaceutics) degree in 2011 and 2014 at university of Sargodha and The Islamia University of Bahawalpur. He is now Ph. scholar under the supervision of Dr. Asadullah Madni in the faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Pakistan. His research focus lies in the formulation of nano-carriers for the delivery of chemotherapeutic agents. Recently, he worked as a visiting scholar under the supervision of Dr. Helder A. Santos, in the Division of Pharmaceutical chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland and working on the fabrication of Lipid polymer hybrid nanoparticles for the targeted delivery of anticancer drugs
Abstract:
Lipid-polymer hybrid nanoparticles (LPHNPs) are emerging platforms for drug delivery applications. In the present study, methotrexate loaded LPHNPs consisted of PLGA and Lipoid S100 were fabricated by employing a single-step modified nanoprecipitation method combined with self-assembly. A three factor, three level Box Behnken design using Design-Expert® software was employed to access the influence of three independent variables on the particle size, drug entrapment and percent drug release. The optimized formulation was selected through numeric optimization approach. The results were supported with the ANOVA analysis, regression equations and response surface plots. Transmission electron microscope images indicated the nanosized and spherical shape of the LPHNPs with fair size distribution. The nanoparticles ranged from 176−308 nm, which increased with increased polymer concentration. The increase in polymer and lipid concentration also increased the drug entrapment efficiency. The in vitro drug release was in range 70.34-91.95% and the release mechanism follow the Higuchi model (R2=0.9888) and Fickian diffusion (n<0.5). The in vitro cytotoxicity assay and confocal microscopy of the optimized formulation demonstrate the good safety and better internalization of the LPHNPs. The cell antiproliferation showed the spatial and controlled action of the nanoformulation as compared to the plain drug solution. The results suggest that LPHNPs can be a promising delivery system envisioned to safe, stable and potentially controlled delivery of methotrexate to the cancer cells to achieve better therapeutic outcomes
Mizuki Mori
Kanagawa institute of Technology,Japan
Title: Cytotoxicity Evaluation Of Nanodiamond Doped With Ethidium Bromide
Biography:
Mizuki Mori was received a bachelor’s degree in Engineering from Kanagawa Institute of Technology, Kanagawa Japan, in 2018. She is in the 1st year of master’s course in an applied chemistry division. She researches about mechanism of genotoxicity of EtBr related compiunds, and now investigates the cytotoxicity of EtBr adsorbed ND
Abstract:
Nano diamond (ND) has higher biological compatibility than the other carbon based nano particles. Because modification of surface functional groups of ND is relatively facile, it is often used as an efficient-carrier of medicinal drugs. In this study, we examined surface modification of both positively charged ND (pND) and negatively charged ND (nND) with ethidium bromide (EtBr) and their biochemical characters.
After alkali treatment of pND and nND, they were mixed with EtBr (weight ratio ND:EtBr=5:1), respectively, and were allowed to stand at the room temperature. Based on the UV absorbance measurement of the supernatant, EtBr was found to be adsorbed on pND and nND with efficiency of 22% and 95%, respectively.
nND-EtBr was revealed to show remarkable cytotoxicity over a dose of 6.25 μg/ml (EtBr concentration was calculated around 1.19 μg/ml) for 48hr treatment to lung cancer cell line(A549), with cell viability of 56%. In a similar manner, effects on the hamster normal lung cell line (CHL/IU)was also evaluated and remarkable cytotoxicity was obtained when nND-EtBr was exposed at 12.5 μg/ml (EtBr concentration was calculated around 2.38 μg/ml) for 48hr treatment with cell viability of 63%. Cytotoxicity of nND itself was also confirmed to both cell line, but their viability was higher than that of nND-EtBr. Among pND and pND-EtBr, we didn’t confirm the difference of cytotoxicity. Moreover, at the concentration of 25 μg/ml nND-EtBr (EtBr=4.75 μg/ml), we also confirmed the fluorescence emission derived from EtBr in cytoplasm of living cell.
As results, we revealed that nND-EtBr complex introduced the higher cytotoxicity than free EtBr and intant ND. And, we confirmed that this complex was penetrated in the living cell. Mechanism of cytotoxicity is now under investigation.
Houman Alimoradi
University of Otago, New Zealand
Title: Synergistic Anti-Cancer Effect Of Stable Nitric Oxide Releasing Nanoparticles, SMA-Tdodsno And Doxorubicin.
Biography:
Houman Alimoradi is a PhD candidate at the Department of Pharmacology and toxicology, University of Otago. Houman has MSc. In Medical Toxicology and a Bachelor in chemistry and his research interest focuses on two major categories: 1) Synthesis of stable and stimuli-responsive nitric oxide donors for intelligent therapy of disease such as cancer. 2) Challenging problems in the delivery of therapeutic agents notably in cancer by (i) regulation of hypoxia and redox balance of cells (ii) synthesis of redox and hypoxia responsive nanocarriers.
Abstract:
Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutic in hypoxic regions of tumor, low cell membrane penetration and low lysosomal escape remain formidable challenges to the enhanced permeability and retention (EPR) effect based therapeutic systems. In order to overcome this limitations we have developed a stable nitric oxide (NO) releasing nanoparticles (NPs) named as SAM-tDodSNO and used it in combination with Doxorubicin (Dox) loaded NPs (SMA-Dox), and their effects on cell proliferation, induction of apoptosis, the changes of lysosomal membrane permeabilization and mitochondrial membrane potential, and tumor growth were studied. Combination of SMA-tDodSNO to Dox showed a synergistic anti-proliferative effect in 4T1 breast cancer cells, and when used in xenografted mice it resulted more than 5.5 folds reduction in tumor size compared with Dox alone. We also found, the SMA-tDodSNO could enhance the endocytosis of SMA-Dox and inhibit Dox efflux from the cells resulting higher concentration of Dox in the cells. Local administration of SMA-tDodSNO in tumor area increased the concentration of Dox in tumor when combined with free Dox or SMA-Dox. SMA-tDodSNO promoted the lysosomal membrane permeabilization and the reduction of mitochondrial membrane potential induced by doxorubicin, and resulted enhanced intracellular calcium concentration. In conclusion, the SMA-tDodSNO as novel NO releasing NPs showed significant cytotoxicity in in breast cancer cells and was able to decrease the tumor growth and potentiated the anticancer potency of Dox both in vitro and in vivo models. Due to NO release it enhanced the endocytosis of a Dox loaded NPs and increased permeability of endosomal membrane hence facilitate the escape of the NPs, and inhibited Dox efflux from the cells.
Rayan Sabra
University of Nottingham, Malaysia
Title: A novel approach toward mucoadhesive and tumour targeting curcumin nanoparticles for colon cancer treatment.
Biography:
Abstract:
Colon cancer is a crucial health problem worldwide. The current interventions combining surgery and chemotherapy have only partially addressed the issue of ineffectiveness and recurrence in patients [1]. Traditionally most anticancer drugs are administered intravenously even for remote cases as in colon cancer, where residential presence of the anticancer drug at the colon is an obvious desirability. Thus, encapsulating drug loaded oral formulations that offer cancer-targeting capability are a promising alternative to improving treatment of colon cancer, whereby localised drug concentration is increased and side effects are minimised [2]. Nanoparticles offer a rational choice due to its large surface area to volume ratio, but should withstand the milieu of the upper gut and deliver its cargo at the colon. In this view, we have developed a modified pectin-chitosancurcumin nanoparticle system (MCPCNPs) (Figure 1) for targeted delivery of curcumin to the colon. The MCPCNPs presented high mucoadhesion propensity in simulated colonic media and minimal at pH 1.2 (stomach). We further enhanced the MCPCNPs by coupling contamumab antibody that target the death receptor (DR5) present on the tumour surface, through a two-step carbodiimide (EDC) approach. The in vitro evaluation of the conjugation was examined using some available analytical techniques, while the conjugation efficiency was confirmed via the micro-bicinchoninic acid assay. The in vitro cytotoxicity and cellular apoptosis assays of the composite nanoparticle-antibody-curcumin-delivery system are being studied currently. In general, the data obtained so far strongly suggests that the formulated mucoadhesive, targeted curcumin-loaded nanoparticles have the potential to be applied as an orally deliverable colon cancer treatment.
Anand Selvaraj
Kaohsiung Medical University,Taiwan
Title: Design A Benzotriazole Linker For Solid-Phase Synthesis Of Peptide Decorated Dendrimer Conjugate As Drug Carrier
Biography:
Anand Selvaraj received his Master’s degree from VIT university, Tamil Nadu, India in 2008. He then worked at Syngene International Ltd, Bangalore, India, for two years and worked on the small molecules. Anand completed his PhD studies under the guidance of Dr. Chai-Lin Kao at the Kaohsiung Medical University in 2018. His research involve design an efficient linker for C-terminal modification and On resin ligation (ORL): synthesis of various peptide analogues such as peptide thioester, branched and cyclic peptide, and also peptide decorated dendrimer for drug delivery strategies.
Abstract:
Peptide decorated dendrimers have been found as an efficient drug delivery vehicle. However, tedious preparation prevents their further development. One synthetic difficulty is the low conjugated efficiency, which is associated with the high steric hindrance of dendrimers. Herein, we describe a new efficient approach for the synthesis of peptide-functionalized dendrimers using 4-amino-3-nitrobenzoic acid (ANB) resin. This approach involves the direct solid phase synthesis of the peptide on a 3, 4-diaminobenzoic acid (Dbz) unit as a linker attached to Rink-amide resin. Mild cyclization of o-aminoanilide with treatment of isoamylnitrite yields a highly active benzotriazole that efficiently reacts with nucleophile to give corresponding adducts. In this investigation, dendrimers as nucleophile directly reacted with on-resin peptide to generate peptide-functionalized dendrimers in a short timeframe. The obtained peptide-decorated dendrimers were encapsulated with anti-cancer drugs and dye. In this study, we develop an enzyme responsive peptide-dendrimer–drug complex based nanomaterial as a potential drug delivery vehicle for cancer chemotherapy.
Janet Tan Sui Ling
University of Nottingham Malaysia Campus, Malaysia
Title: Mucoadhesive Chitosan-coated Nanostructured Lipid Carriers (NLC) for Oral Delivery of Amphotericin B
Biography:
Janet Tan Sui Ling has completed her Master of Pharmacy (Mpharm) in 2015 from University of Bath, United Kingdom with first class honours. She was also awarded Royal Pharmaceutical Society Prize for Best Overall Third Year Student (2014), Pfizer Prize for Best Medicine Design in Third Year (2014), Vectura Prize for Best Advanced Drug Delivery (2015) and AstraZeneca Prize for Best in Cancer (2015). She contiuned her studies in PhD in University of Nottingham Malaysia Campus in 2015 and currently, is in her second year of study. She has won the Best PGR presenter in UNMC PG Link ’17 Conference.
Abstract:
Oral delivery of amphotericin B (AmpB) remains challenging due to physicochemical properties of AmpB such that it results in meagre bioavailability (0.3%). In an advanced formulation, 1) nanostructured lipid carriers (NLC) were formulated as they can accommodate higher levels of cargoes and restrict drug expulsion and 2) a mucoadhesion feature was incorporated to impart sluggish transit along gastrointestinal tract and hence, maximize uptake and improve bioavailability of AmpB. Chitosan-coated and naked AmpB-loaded NLC formulations were successfully formulated. Physical properties of the formulations; particle size, zeta potential, encapsulation efficiency and mucoadhesion as well as the effect of the variable pH on the integrity of the formulations were investigated. The particle size of freshly prepared AmpB-loaded NLC was 163.1 ± 0.7 nm, with a negative surface charge and remained essentially stable over 120 days. Adsorption of chitosan caused a significant increase in particle size to 348.0 ± 12 nm with the zeta potential reverts towards positivity. The incorporation of chitosan increased the encapsulation efficiency significantly by 5%, to 99.3 ± 0.15% and observed lower expulsion of AmpB after exposure to variable of pH conditions. The mucoadhesiveness of the ChiAmpB NLC formulation was observed in both acidic (pH 5.8) and near-neutral pH (pH 6.8) conditions as opposed to AmpB-loaded NLC formulation. Hence, the incorporation of chitosan into the NLC formulation did not only impart mucoadhesive property but also protected against the expulsion of AmpB which makes it well-primed as a potential oral delivery system for AmpB.
Andra-Sorina Tatar
Babes-Bolyai University, Romania
Title: Novel theranostic agents against Acute Lymphoblastic Leukemia: CD19-targeting Gold Nanourchins
Biography:
Andra-Sorina Tatar has received her BSc in Biochemistry and in Physics and the MSc in Molecular Biotechnology from the Babes-Bolyai University, Cluj-Napoca, Romania. Having an interdisciplinary background, she started her PhD work focusing on the design of antibody-conjugated nanoparticle-based systems and their application for the spectroscopic detection of circulating tumor cells and treatment of hematological diseases
Abstract:
Acute Lymphoblastic Leukemia (ALL) is the first and second most common malignancy in children and adolescents. With a broad range of genetic causes, this disease may appear with various protein expression profiles, routing the researchers towards a more promising patient-specific treatment plan.
Through our work, we aim to develop a nano-tool which is targeted towards the ALL specific CD19 surface protein via the strong antibody-antigen interaction. Specifically, we developed a gold nanourchin based vehicle for antiCD19 using a surfactant free seed mediated synthesis protocol. By employing the Trypan Blue dye exclusion method, we show the highly significant cytotoxic effect of our targeted particles against CCRF-SB B-lymphoblastic leukemia cells as compared to the non-targeted ones, as well as to the free antibody molecule. Cell cycle analysis using Flow Cytometry, metabolic activity investigation by MTS assay, and morphological analysis by TEM contribute with valuable additional insights to the conclusion that the antiCD19 targeted nanourchins accomplish their therapeutic duty. Additionally, these anisotropic nanoparticles possess interesting optical properties such as plasmon resonances in the NIR domain and the efficient amplification of the nearby electromagnetic field, which provide them with valuable imaging features and the capability of being used as spectroscopic tags inside living cells.
Acknowledgement: This work was supported by the project PN-II-RU-TE-2014-4-2426.
Biography:
Mahdieh Heydarigoojani has completed her bachelor at the age of 23 years from Science and Research islamic azad university in Iran and she is master student of biomedical engineering at TU University of Vienna. This reaserch has been done by collaboration with Tarbiat modares University of Iran .
Abstract:
In Atherosclerosis, vessels wall getting narrow and stiff. It is refers to buildup LDL(low density lipoprotein) and as a result, blood and nutrition can not pass through artery. Also Endothelial cells are injured and smooth muscle cells immigrate into the Intima. Therefore anticancer drugs would be appropriate choice for treatment. Curcumin and Docetaxel showed anti inflammatory and anti proliferative effects respectively. But their clinical application has been limited due to the fact that hydrophobicity and poor bioavailability. For this reason a potent mPEGPCL micelle system was synthesized and release profile of Curcumin and Docetaxel from drug- loaded micells was characterized.
Hippolyte Durand
University of Grenoble Alps,France
Title: The use of cellulose nanofibrils from wood as an innovative drug carrier in medical devices
Biography:
Hippolyte Durand is doing its PhD in Univ. Grenoble Alps at LGP2 (Laboratory of Pulp and Paper Science and Graphic Arts) located in Grenoble, France. He is has a strong background in cellulose and nanocellulose science. He is part of the CELLICAL project which aims at developing new medical devices for wound healing. The use of cellulose nanofibrils is the corner stone of the research done by the consortium of CELLICAL project.
Abstract:
For several decades now, Cellulose Nanofibrils (CNF) from wood are of high interest in many research fields. They turned out to have high specific area, low density, excellent mechanical properties and chemical reactivity, besides their character of renewable resource. Highly entangled networks of such nanofibrils (5-20nm in width and 1-5µm long) are formed easily, resulting in films with high mechanical and barrier properties that make them interesting candidates for a number of applications, as seen recently in the medical field. The surface functionalization of these nanofibrils allows researchers to bring new properties to this wonderful material in order to incorporate it in new innovative bio-based products. The purpose of this work is to use CNF as a drug carrier in order to develop bioactive medical devices. CNF surface were first functionalized with drugs either by covalent or non-covalent binding and then incorporated in a matrix of collagen based material or used as films. Both types of samples, composites and films, are produced by solvent casting in controlled conditions. The drug release study of these medical device prototypes was conducted in-vitro in different model release medium such as PBS and enzyme containing solutions and gels. The use of CNF as drug carrier permitted to extend the duration of the drug release, resulting in an innovative and controlled drug delivery. This project intends to bring new bio-active products to the market of medical devices in order to ease post-surgery treatments and improve wound healing
- Advanced Nanomedicine
Location: Radisson Hotel Narita
Session Introduction
Kesavan Karthikeyan
Guru Ghasidas Central University,India
Title: Chitosan Based Positively Charged Mucoadhesive Nanocarriers for Ocular Drug Delivery
Biography:
Dr. K. Kesavan is a well-versed nanotechnologist, with expertise in developing nanoparticulate systems for delivering lipophilic drugs to eye for the treatment of ocular diseases. His group developed HP-β-CD-based mucoadhesive pH induced hydrogel system and mucoadhesive microemulsion of dexamethasone for ocular delivery to treat uveitis in rabbit eye model. His research group recently studied the ion activated hydrogel system and phase transition microemulsion for ocular delivery to treat keratitis in rabbit eye model. Recently his group published a paper in ocular selfmicroemulsifying drug delivery system of prednisolone for effective treatment of uveitis in rabbit eye model. Currently, his group working on the development of the nanoparticulate drug delivery systems for ocular drug delivery, which would offer the advantages of decreased dose and dosage regimen, sustained release, improved patient compliance, and enhanced safety profile.
Abstract:
Cornea and conjunctiva carry a negative charge upon their surface, due to the presence of negatively charged mucus residues on the outer side of their membranes, and to selective active ion pumps. Ocular surface should thus be selective to positively charged delivery systems that interact with cells, leading to increased drug permeability and prolonging the pharmacological effect. Chitosan (CS), as a unique positively charged polysaccharide, has been one of the most popular biopolymers for development of drug delivery systems for various applications, due to its promising properties, including high biocompatibility, excellent biodegradability, low toxicity, as well as abundant availability and low production cost. In fact, an ionic interaction between the positively charged amino groups of CS and negatively charged sialic acid residues in mucus has been proposed as the mucoadhesion mechanism. Since last decade, increasing attention has been attracted by delivery systems fabricated from natural biopolymer-based polyelectrolyte complexes (PEC), formed by electrostatic interactions between two oppositely charged biopolymers. The preparation of nanocapsule via complex coacervation method is based on the PEC through the electrostatic interactions between cationic and anionic polymers, resulting in the formulation of insoluble spherical beads or capsules. Due to the protonation of amino groups on the backbone, CS becomes a cationic polyelectrolyte in acidic medium, which could form PEC with negatively charged polyelectrolytes, resulting in various applications. In recent years, positively charged liposomes and nanoemulsions have been used as drug carriers. CS is suitable for formulation of mucoadhesive cationic nanoemulsion because it is positively charged, making it able to adhere to the negatively charged oil globules in nanoemulsion and is soluble in diverse acids and able to interact with polyanions to form complex and nanogel. This is an effort to summarize the recent developments in the area of CS based cationic mucoadhesive nanocarriers for ocular drug delivery.
Virendra Gajbhiye
Agharkar Research Institute,INDIA
Title: Nanocarriers-mediated siRNA delivery for treatment of cancer
Biography:
Virendra Gajbhiye completed his M. Pharm and Ph.D. from Dr. H. S. Gour University, Sagar, India. He was a postdoctoral research fellow at Wisconsin Institute for Discovery, University of Wisconsin, Madison, WI, USA and Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA. Currently, he is working as a Scientist at Nanobioscience Group, Agharkar Research Institute, Pune, India. Virendra Gajbhiye has his expertise in developing multifunctional nanocarriers and their use in nanomedicine and theranostics, targeted delivery of drug/siRNA/miRNA for cancer therapy, and tissue engineering. He has extensively worked on drug targeting to brain. Currently, he is extensively working on delivery of siRNA/miRNA for treatment of breast cancer.
Abstract:
Cancer is one of the major health problems worldwide and the number of cancer cases is projected to increase by 50% by 2030. Current therapies include surgery, chemotherapy, radiation and hormonal therapy which are also used sometimes in combination to lower the risk of reoccurrence. These therapies used till date are followed by various side effects and disadvantages. Hence, newer and targeted therapies are required. One of the ways is to explore siRNA therapy that works on RNA interference mechanism. siRNA of 21-25 nucleotide long help in turning off expression of cancerous gene by directing degradation of selective mRNA. The major bottleneck in siRNA therapies is their delivery to desired cell type. siRNA does not readily cross the cellular membrane because of their negative charge and size. Moreover they are very sensitive to nuclease degradation, thus posing serious challenges in efficient delivery. Nanotechnology has been drawing a huge attention for successful and targeted delivery of siRNA. Hence we thought of using nanotechnology based vector which can be used to deliver siRNA efficiently. Multifunctional cationic dendrimers, Mesoporous silica nanoparticles (MSNPs) and other NPs are being used by use to deliver siRNA specifically to breast as well as prostate cancer cells. Our study shows that a unimolecular dendritic system (Figure 1) conjugated with luteinizing hormone releasing hormone (LHRH) analogue was able to deliver siRNA specifically to LHRH receptor overexpressing breast as well as prostate cancer cells. In one of our recent study, we observe that siRNA delivery can be achieved via unimolecular dendrimers conjugated with peptide by targeting integrin receptors of breast cancer cells. Also, cationic cobalt ferrite nanoparticles synthesized in our lab was able to successfully deliver siRNA in breast cancer cells. Similarly, our latest results show that multifunctional MSNPs (Figure 2) can be effectively use for the treatment of drug resistant breast cancer cells.