Scientific Program

Conference Series LLC Ltd invites all the participants across the globe to attend 2nd International Conference and Exhibition on Nanomedicine and Drug Delivery Tokyo, Japan.

Day 2 :

Keynote Forum

Jyh-Ping Chen

Chang Gung University, Taiwan

Keynote: Thermosensitive Magnetoliposome Nanodrugs for Cancer Therapy

Time : TBA

NanoDelivery 2018 International Conference Keynote Speaker Jyh-Ping Chen photo
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:

Thermosensitive Magnetic Liposomes Were Developed For Controlled Release Of A Thrombolytic Drug And Anticancer Chemical/Gene Drugs For Thrombolysis And Glioma Treatment. As The FDA Has Approved The Application Of Liposome-Encapsulated Anticancer Drugs In Clinical Practice, Magnetic Liposome Formed By Entrapping Iron Oxide Magnetic Nanoparticles (MNP) In Phospholipids Could Be A Safe Platform For Drug Delivery. By Incorporating (Phospholipiddipalmitoylphosphatidylcholine, DPPC) With A Melting Temperature (Tm) Slightly Above The Physiological Temperature In The Liposome, The Thermosensitive Magnetic Liposome Was Designed For Controlled Release Of Entrapped Drugs Subject To Temperature Increase From 37 Oc To 43 Oc Or Through A Hyperthermia Effect Induced By An Alternating Magnetic Field (AMF). In Addition, The Co-Entrapped MNP Could Be Used For Magnetic Targeted Delivery Of The Cargo In The Liposome Under The Guidance Of A Magnet. The Temperature-Sensitive Liposomes Were Synthesized From DPPC, Distearolyphosphatidylethanolamine-N-Poly(Ethylene Glycol)2000 (DSPE-PEG2000), Cholesterol (CH) And Bis-Dodecyl Dimethyl Bromide (DDAB). Citric Acid Modified Iron Oxide MNP Were Encapsulated Into The Liposome Along With Anticancer Chemical Drug (Irinotecan, CPT11)/Gene Drug (SLP2 Shrna) To Prepare Thermosensitive Cationic Magnetic Liposome-CPT11-Shrna (TCML-CPT11-Shrna). The Composition Of Phospholipids Was First Optimized Followed By Physicochemical Analysis By DLS, Cryo-TEM, FTIR, TGA, DSC, SQUID, Zeta Potential And XRD. Enhanced Drug Release Was Confirmed By Temperature Change From 37 Oc To 43 Oc Or In The Presence Of An AMF. 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.

 

Keynote Forum

Shaoqin Sarah Gong

University of Wisconsin ,USA

Keynote: Unimolecular Nanoparticles for Targeted Drug Delivery

Time : TBA

NanoDelivery 2018 International Conference Keynote Speaker Shaoqin Sarah Gong photo
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

  • Young Research Forum
Location: Radisson Hotel Narita

Session Introduction

Mizuki Mori

Kanagawa institute of Technology,Japan

Title: Cytotoxicity Evaluation Of Nanodiamond Doped With Ethidium Bromide
Speaker
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.

 

Speaker
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.

 

 

 

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.

Speaker
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.

 

Speaker
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.

 

Speaker
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

Speaker
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.

Speaker
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.

Speaker
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.

Speaker
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
Speaker
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.

Speaker
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 DiscoveryUniversity of Wisconsin, Madison, WI, USA and Department of Biomedical EngineeringOregon 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 theranosticstargeted 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 surgerychemotherapyradiation 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.  

  • Drug Delivery Research
Location: Radisson Hotel Narita
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. 

 

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.

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.

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