International Conference and Exhibition on Nanomedicine and Drug Delivery May 29-31, 2017 Osaka, Japan

Seongjae Jo studied control and measurement theory at the Department of Control and Instrumentation Engineering at Korea University. Among various subjects, He was interested in sensors and went to graduate school to study nano and biosensors. He is currently studying for the 5th semester of graduate school as a master and doctor Integrated course. He is studying sensing methods using optics such as absorbance, Raman scattering, and fluorescence, and he is also studying the synthesis of gold nanoparticles for optical applications. His study is supported by the National Research Foundation of Korea (NRF) under Grant no. NRF-2015R1A1A1A05027581 and Korea University Future Research Grant.

As the modern technology has developed, the problem to toxicity of nano-scale materials continues to rise, so it has emerged as an important research project to detect the toxic agents. In particular, according to a recent study, small amounts of copper ions increase the growth rate of the tumor, so it is important to detect a low concentration of copper ions. A conventional method for detecting ions is a use of inductively coupled plasma (ICP) that is expensive and has a hassle things like preprocess of the samples and stabilization of the plasma which is necessary. However, the use of localized surface plasmon resonance (LSPR) is one of the techniques using the optics which can easily and quickly detect materials on the substrate in real time. The substrate and chelators, antibodies, aptamers or ligands are conjugated, can bind the desired materials like ions, proteins, even enzymes and genes. In this study, we made nanoplasmonic substrates using gold nanorods and D-penicillamine (DPA). D-penicillamine (DPA) is easy to conjugate with gold due to thiol group. But it is a chelator of the copper, so the DPA conjugated to the substrate is separated from the substrate and bonded to the copper II ions. Copper ion could be detected up to 100 picomolar (pM) concentration by using the nanoplasmonic substrate. It shows a unique selectivity for copper II ions. And we were able to detect copper in human blood-like environment. Based on this study, not only copper II ions but also other ions can be detected by making the substrate that can be more quickly and easily monitored for ions.

Yu Yan has completed her bachelor at the 21 years from South Medicine University of China and now she is a master whose major is histology and anatomy and from Medicine school of Jinan University. She has published 3 papers in reputed journals in 2016.

Dexamethasone (Dex) is widely used to treat chronic inflammatory diseases in the clinic. Increasingly, there is more attention being paid to the side effect of Dex. In this study, we investigated the involvement and mechanism of Dex exposure in accelerating mineralization during long bone formation. We first determined that Dex exposure could accelerate long bone mineralization in vivo, but there was no apparent difference between control and Dex-treated in the phalanges model in vitro. Next, we established that Dex exposure promoted angiogenesis in the chick yolk sac membrane (YSM) model. In addition, it increased HUVEC cell proliferation and migration in culture. We found that Dex could enhance angiogenesis when phalanxes were cultured on chick chorioallantoic membrane (CAM) and correspondingly increased the expression of angiogenesis-related genes in the phalanxes. Furthermore, we also revealed that Dex exposure reduced the number of osteoblasts and simultaneously increased the number of osteocytes in ex vivo cultured phalanges. Runx-2 and Col10α1 expressions were up-regulated by Dex exposure, indicating that Dex exposure accelerated the terminal differentiation of osteoblasts. Lastly, we demonstrated that MC3T3-E1 cells cultured in the presence of Dex accelerated their mineralization. In summary, we have shown that the ability of Dex to initiate angiogenesis is the mechanism that allows it to accelerate mineralization during long bone formation.

Atinderpal Kaur is persuing her PhD from Jaypee Institute of Information Technology, Noida (Jaypee University) from department of Biotechnology. She has published 2 papers and submitted 4 papers (under reveiw) in reputed journals. She has worked as Assistant professor in reputed college of Pharmacy for more than 3 years. Currently She is working as Research Fellow in a funded project by Department of Biotechnology, Govt. of India, New Delhi, India.

Polyphenon 60 (P60) and Curcumin (CUR) were loaded in a single nano emulsion system and their combined antibacterial action was studied against uropathogenic Escherichia coli. To enhance bioavailability at target organs and to inhibit enzymatic degradation in Gastric Intestinal Tract, vaginal route of administration was explored. P60+CUR Nano emulsion (NE) was formulated by ultra-sonication and optimized using Box-Behnken design. Optimized NE showed Z-average of 211.2 nm, polydispersity index 0.343 and zeta potential -32.7 mV. Optimized P60+ CUR NE was characterized for stability and transmission electron microscopy (TEM) and it was observed that NE was stable at 4˚C for 30 days and monodispersed in nature with particle size in the range of 195-205 nm. P60+ CUR NE was further formulated to gel and characterized by viscosity parameters and in-vitro permeation studies. In vitro drug release studies in simulated vaginal media showed maximum release (84±0.21%) of curcumin within 5 h and (91±0.16%) of P60 within 8 h. Both the drugs maintained sustain release up to 12 h. To investigate the transport via intravaginal route, gamma scintigraphy and biodistribution study of P60+CUR NBG was performed on Sprague-Dawley rats using 99mtechnetium pertechnetate for radiolabeling to P60 molecule. Following intravaginal administration, P60+CUR NBG dispersed in kidney and urinary bladder with (3.07±0.15) and (3.35±0.45) percentage per gram after 3 h, respectively and remained active for 12 h. Scintigraphy images and biodistribution findings suggested that the P60+CUR NBG given by intravaginal route led to effective distribution of actives in urinary tract to eradicate urinary tract infection.

Weiam is currently a PhD candidate at the University of Calgary, Canada. She has two publications thus far in peer reviewed journals (J. Phys. Chem. B. and Colloids Surf. B). She has a B.Sc in Biological Sciences with a minor in nanoscience

The pulmonary route offers many advantages for drug delivery such as the high surface area and the close proximity to the blood circulation. The air-blood barrier of the alveoli in the lungs is around 500 nm thick. Above the epithelium cells of the alveoli lies a thin aqueous layer with a thickness of 50-80 nm. A monolayer of phospholipids, natural lipids and few proteins called the lung surfactant (LS) adsorbs onto this aqueous film. The major phospholipid classes include phosphatidylcholines and phosphatidylglycerols. One of the main roles of the LS is to reduce the surface tension experienced in the lungs during breathing cycles in order to prevent lung collapse. From the perspective of pulmonary drug delivery, the LS is the first point of interaction for the drug carriers. With the advancements of nanomedicine, nanoparticles (NPs) became highly relevant as novel drug delivery systems. In particular, there is a great scientific interest for the use of biodegradable NPs for pulmonary delivery route. The objective of our work is to develop a biomimetic model of the LS and then study the effects upon interaction with NPs. Therefore, we focus on understanding the mechanism of interaction between biodegradable polymeric NPs with the biomimetic model of the LS and test whether the stability and lateral architecture of LS is affected. These measurements and are done by using Langmuir monolayers at the air-water interface and imaged using Brewster angle microscopy. Results show that the film stability upon compression is not affected, but there are significant changes in the lateral domain organization of the LS upon NP addition. This work is significant because it helps understand the mechanism of NP-LS interaction and will provide an in-vitro screening approach to assess nanotoxicology.

Mandana Emamzadeh (B.Pharm, M.Sc.) is PhD student in cancer nanomedicine at UCL School of Pharmacy, London. Her area of focus is thermo-responsive smart nano-carriers for drug delivery. She has her expertise in thermo-responsive polymeric micelles and polymer modified thermo-responsive liposomes. She has been synthesizing novel nano-carries which are able to co-deliver combination of anti-cancer drugs. Her research is expanding by incorporation of gold nanoparticles to synthesize further stimuli-responsive nano-carriers.

Pancreatic cancer is one of the most lethal malignancies with very low survival rate. Despite having low incidence rates it ranks as the fifth most common cause of cancer mortality. The aim of chemotherapy in pancreatic cancer is to increase the survival time and the quality of patient’s life. However, systemic toxicity occurs due to the distribution of the drugs non-specifically in the body which affect both normal and tumor cells. Targeted chemotherapy can be achieved by protecting the anti-cancer drugs in systemic circulation and delivering them to the tumor site by the use of nanoparticles. Thermo-responsive polymeric micelles are nanoparticles that consist of a hydrophobic core in which lipophilic drugs can be encapsulated and a thermo-sensitive hydrophilic corona that prevents the interaction of the carriers with the blood proteins and also allows for thermally triggered drug release specifically at the tumor sites. In this research, novel thermo-responsive block copolymers, poly[(di(ethylene glycol) methyl ether methacrylate-co-poly(ethylene glycol) methyl ether methacrylate300)-b-poly(2-ethylhexyl methacrylate)] [poly(diEGMA-co-OEGMA300)-b-PEHMA], were prepared by reversible addition fragmentation chain transfer (RAFT) polymerization. Poly(diEGMA-co-OEGMA300)-b-PEHMA self-assembled into micelles which were co-loaded with two anti-cancer drugs, squalenoyl-gemcitabine [(Sq-GEM), a hydrophobized amino-protected derivative of gemcitabine (GEM)] and paclitaxel (PTX) in order to exert combined and synergistic anticancer activity. The drug loaded micelles had a low critical micelle concentration (20 mg/L) and showed high colloidal stability. The drug release studies showed a thermally controlled profile where the release increased 2 orders of magnitude above the polymers’ lower critical solution temperature (LCST) at 40°C for both sq-GEM and PTX. In vitro cytotoxicity assays (MTT assay) on MiaPaCa-2 pancreatic cancer cell line showed a synergistic effect of combinational co-delivery of sq-Gem and PTX with significant decrease of cells’ viability compared to cells treated with each drug separately or

Nur Akib currently a PhD candidate at Kemaraya Kendari Sulawesi Tenggara, Indonesia.

Theophylline has 8 hours of half life and is used for chronic lung disorder treatment, especially asthma. Oral theophylline is not always recommended because it requires frequent administration. The entrapment drugs in a vesicle have shown improved delivery at the targeted site and also have reduced the side effects thus increase patient compliance. Ethosomes are lipid vesicular carriers that contain high concentration of ethanol which provide better penetration of drug into the skin. This study was aimed to obtain the stable formula of gel. Theophylline ethosomes were prepared by hot method (40oC). The compositions of theophylline ethosomes were phosphatidilcholine (2%), ethanol (40%), propylene glycol (10%) and distilled water up to 100%. Gel formulation was optimazed by varying concentration of the carbomer base (0.5; 1; 1.5; and 2%). Stability test of theophylline ethosomal gel was performed before and after the cycling test with different temperature (5o C and 40o C). The obtained value of the viscosities before cycling test were 350-1.300 cP and after cycling test were 425-1300 cP; the pH values before cycling test were 7.19-5.97 and after cycling test were 7.39-6.26; and the dispersive values before cycling test were 9.5-5.15 cm2 and after cycling test were 9.1-5.1 cm2. It was concluded theophylline ethosomal gel with 25 of carbomer has the best stability.

Sirirat Boondireke received Bachelor’s degree in Biotechnology (2007) and Master’s degree in Microbiology (2010). Currently, she is a Ph.D. candidate in Biomedical Science Program at Department of Microbiology, Faculty of Medicine, Srinakharinwirot University, Thailand. She has been receiving a Royal Golden Jubilee Ph.D. Scholarship awarded by the Thailand Research Fund under the Office of the Prime Minister, the Royal Thai Government since 2012. She also received the Ph.D. grant from the French Government to carry out a part of her Ph.D. research at Laboratory of Macromolecular Chemical Physics (LCPM), Université de Lorraine, France in 2014 and 2015. Her interdisciplinary Ph.D. project has focused on the development and synthesis of polymeric nanoparticles for the encapsulation of anticancer agents with a targeting ligand attached on their surface to induce specific recognition and accumulation at cancerous cells/tissues. Sirirat has interests in drug delivery system, targeting, nanomedicine for cancer therapy and biomedical research.

Statement of the Problem: Cancer refers to a group of over 100 distinct diseases which result in severe illnesses and eventually leads to death. Though treatment by chemotherapy in cancer patients appears to be effective against cancerous cells. It is hindered by limitations in drug absorption, accumulation and drug targeting, therefore normal rapid-proliferating cells are always destroyed and lead to death. Drug delivery system is the clue to bring the anticancer drug to the cancer cells target. Polymeric nanoparticles (NPs) is a choice of vehicle in drug delivery system in order to enhance drug absorption, accumulation, thus prevent drug loss, as well as improve sustained release of drug in cancerous tissues. However, NPs properties, such as, biodegradability, biocompatibility, solubility in aqueous or dispersion stability and drug release profile, are relied on materials used as components. The purpose of this study is to focus on encapsulation of monomyristin (MM) which was tested to have the antiproliferative activity against cervical cancer (HeLa) cells using poly(lactic acid) (PLA)-based nanoparticles (PLA NPs) with hydrophobically-modified dextran grafting for preparing drug-loaded polymeric NPs for drug delivery. Methodology & Theoretical Orientation: In the present study, dextran was grafted with phenoxy group at different levels of phenoxy. The modified dextran was used to develop NPs with PLA using emulsion/solvent evaporation method with different sonication powers. The NPs components, stability, size and aggregation were checked. Findings: The result showed that NPs grafted with DexP26 had the least aggregation. This thus implied that DexP26 may serve as a good stabilizer in the synthesis of NPs. Conclusion & Significance: From this study, MM-encapsulated PLA NPs were newly prepared and they could serve as promising/stable carriers for MM delivery.

Chih-Peng Liu is a senior researcher of Biomedical Technology and Device Research Laboratories (BDL), Industrial Technology Research Institute (ITRI). ITRI is a nonprofit R&D organization engaging in applied research and technical services. The vision of BDL is to become a premier global hub for the research and development of innovation-based biomedical technology and medical devices. Liu received his Bachelor of Pharmacy at Taipei Medical University and obtained his MS and PhD in Pharmacology from National Yang-Ming University. He majors and specialties are focused on Pharmacokinetics (PK) and pharmacodynamics (PD) evaluation of drug development. Currently he is a Deputy Project Manager of drug delivery division and responsible for the novel hyaluronan-based nanocarriers development.

Statement of the Problem: Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Current therapeutic approaches in treating HNSCC patients are limited in choice and efficacy, hampered by physiological side effects, as well as risks of recurrence. Even with surgical resection, microscopic tumor may remain and lead to locoregional recurrence. Moreover, systemic chemotherapy cannot effectively reach the lymphatic system without showing dose-limiting toxicities. Therefore, treatment of lymphatic metastasis remains a great challenge. Methodology & Theoretical Orientation: HA/Boc-His/PEG graft copolymers were mixed with cisplatin followed by stirring for 72 h. The mixture was sonicated and purified to form CPHC008. The size distribution and drug release from CPHC008 were evaluated by dynamic light scattering measurement and dialysis method. To evaluate the lymph node delivery, mice were injected intravenously with CPHC008 and cervical lymph nodes were collected to analyze the platinum content by ICP-MS. To investigate the inhibition of lymphatic metastasis, CPHC008 were injected intravenously into mice bearing SAS-LN tumor with cervical metastasis. The cervical nodes were collected to evaluate metastasis by bioluminescence imagine using IVIS. Findings: The particles size and zeta potential of CPHC008 were 200 nm and -30 mV respectively. The drug release behavior from CPHC008 in PBS showed more stable than native HA-based nanoparticles. In vitro cellular binding/uptake demonstrated CPHC008 could target the CD44+ cells. As a result of CD44-targeting, CPHC008 could increase platinum levels in the cervical nodes and inhibit lymphatic metastases significantly. Conclusion & Significance: We have designed a HA-based nanocomplexes to increase platinum levels in the lymphatics, where early metastasis is most likely to occur. This lymphatic delivery platform may offer significant advantages for the use of platinum medicines in the management of locally advanced HNSCC, treating microscopic lymph node disease with better efficacy than current high-dose systemic chemotherapy.

Robert Pola has completed his PhD at the age of 37 years from Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic (IMC). He is the member of Department of Biomedicinal Polymers of IMC. He has published 24 papers in reputed international journals. His research focus is based on synthesis of peptide sequences and preparation of water-soluble polymer conjugates used as drug delivery systems for effective treatment of cancer or for vaccination.

Precise preclinical characterization of new polymeric prodrug candidates is important for understanding the effects of polymer prodrug structure on distribution, controlled drug release and elimination of these carrier systems. In our study, we have demonstrated the enzymatic release of a lysosomotropic model drug inside a tumor using multispectral optical imaging in vivo in nude mice bearing two different colorectal carcinoma xenograft models - HT-29 and DLD-1. We also clearly demonstrated the important role of the molecular weight of a polymeric drug carrier in tumor accumulation and the rate of enzymatic drug release. Our study showed a much higher rate of the model drug release in vivo from a linear (30 kDa) (N-2-hydroxypropyl)methacrylamide (HPMA)- based polymer compared with a high molecular weight branched (170 kDa) polymer conjugate. There was no significant difference in the relative biodistribution in the body between the 30 kDa linear and 170 kDa branched polymers, but the branched polymer circulated much longer. Both copolymers were labeled with two different fluorophores. Dyomics-676 (DY-676) dye was attached to the polymer via an enzymatically cleavable Gly-Phe-Leu-Gly spacer, which represented a lysosomotropic drug model molecule. Dyomics 782 (DY-782) dye was bound to the same polymer backbone via a non-degradable amide bond enabling the tracking of the polymer carrier itself after i.v. application to mice. We hypothesize that the increase in the molecular weight of the polymer prodrug conjugate significantly lowers the rate of release of the model drug due to steric hindrance of the cleavable spacer to enzymes. Acknowledgements: This work was supported by the Ministry of Health of the Czech Republic (grant 16-28594A) and by the Deutsche Forschungsgemeinschaft DFG (MA 1648/8-1; to T. Mueller and K. Mäder).

Eliška Böhmová finished her master’s degree in 2016 at the University of Chemistry and Technology in Prague, Czech Republic. Nowadays she studies her PhD at the Department of Biomedical polymer of the Institute of Macromolecular Chemistry AS CR in Prague. She is 26 years old. The topic of her dissertation thesis is “Targeted polymeric drugs with enhanced penetration into tumor cells”. Her scientific interests are polymer chemistry, solid phase peptide synthesis, design and synthesis of polymer drug delivery systems for treatment of cancer

RGD-based peptides are well known as structures capable of targeting to tumor neovasculature. Recently, actively targeted polymer cancerostatics using linear RGD based peptides has been already described by our group.1 The main aim of the present work is to compare polymer carriers targeted by linear peptide and by branched form of RGD. Scrambled peptide GRDGG was used as a control. This work is focused on preparation of polymer conjugates based on copolymers of N-(2-hydroxypropyl) methacrylamide (HPMA) with comonomers bearing various RGD-based peptides and a fluorescent label cyanine 5.5 attached to the main polymer chain. First, copolymers containing reactive thiazolidine-2-thione (TT) groups with narrow distribution of molecular weights were prepared by RAFT polymerization using dithiobenzoates as chain transfer agents. RGD-based peptide sequences were prepared by standard Fmoc solid phase peptide synthesis using Tenta gel Rink amide resin. Fmoc-NH-PEG(4)-COOH was used as a linker between the peptide and the polymer chain. Coupling of the copolymer with the dye and the peptide via amino groups in an aqueous buffer at pH 8 was monitored by HPLC. The synthesized peptide-polymer conjugates were characterized by SEC. Targeting activity was verified in vitro using human umbilical vein endothelial cells (HUVEC) and human prostate adenocarcinoma cell lines (PC-3) as αVβ3 integrine positive cell lines. Human mammary gland adenocarcinoma (MCF-7) and human prostate adenocarcinoma (LNCaP) cells were used as negative controls. Comparison of each conjugate in terms of endothelium cells targeting efficiency was also monitored. The intended application of these polymer conjugates is selective fluorescent labeling of tumors for endoscopic surgery head and neck carcinomas. Precise visualization of the edge of the tumor is the key factor for removal of the whole tumor without damage of the healthy tissue that often leads to undesired postoperative consequences, e.g. impaired swallowing, articulation or damage of vocal folds. Acknowledgements: This work was supported by Czech Science Foundation, grant 16-17207S and the Ministry of Health of the Czech Republic, grant 16-28594A.

Alena Braunová has completed her PhD in 2006 from Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic (IMC). She is the senior researcher of Department of Biomedicinal Polymers of IMC. She has published 14 papers in reputed international journals, which were cited more than 98 times and she is an author or co-author of more than 40 international conference contributions and abstracts. Her research focus is based on preparation of micellar and water-soluble drug delivery systems for effective treatment of cancer and cancer diagnostics.

Multidrug resistance (MDR) is one of the main causes of imperfect treatment of many types of haematological malignancies and solid tumours. The resistant of cancer cells to current chemotherapy is associated with the overexpression of at least two ATP-dependent efflux pumps (P-gp and MRP1) which participate in the preferential active transport of cytotoxic drugs out of the cells before the therapeutic effect. An inhibition of the overexpressed proteins described before should improve the retention of chemotherapeutics inside tumour cells, and thus a more effective cancer therapy can be achieved. It has been previously found that the high-molecular weight polymer carriers and their polymer-drug conjugates are subject of passive accumulation in solid tumours due to enhanced permeability and retention effect. Here we present design, synthesis and evaluation of physico-chemical and biological characteristics of novel block copolymers serving simultaneously as drug delivery systems and MDR inhibitors were. The amphiphilic character of presented copolymers caused their self-assembling into polymer micelles with an increased hydrodynamic radius in aqueous solutions. Cytostatic drug is bound to the copolymer through a pH-sensitive bond enabling a prolonged circulation in blood, the delivery of drug into solid tumour and controlled release of drug within tumour mass and cells at a decreased pH. The applicability of polymer nanotherapeutics as a drug carrier was confirmed by an in vivo biological evaluation. We observed significantly higher accumulation of micellar conjugates with drug in a solid tumour because of the EPR effect compared with the similar polymer-drug conjugate that do not form the micellar structure or with the parent free drug. MDR inhibition of the copolymers was verified by in vitro tests. In addition, we observed highly increased rate of the uptake of micellar nanotherapeutics within the cells.

Mohd Basyaruddin Abdul Rahman has completed his PhD at the age of 25 years from University of Southampton and postdoctoral studies from Institute of Structural and Molecular Biology, University of Edinburgh. He was the director of Malaysia Genome Institute, and currently the Deputy Dean of Faculty of Science, Universiti Putra Malaysia. His research areas include biocatalysis, protein chemistry, nanobiotechnology and computational chemistry. He has published more than 200 papers in reputed journals and filed more than 20 patents. He is the Fellow of Royal Society of Chemistry and Fellow of Academy of Sciences Malaysia.

Quercetin is a hydrophobic drug commonly studied and used to treat lung cancer. However, poor hydrophilicity leads to low solubility and hinders its application in water-based formulation. Oil-in-water (o/w) nanoemulsion is capable of delivering poorly water-soluble drugs. D-optimal mixture design was used to optimize the particle size of quercetin (QT) nanoemulsions for lung cancer by aerosols delivery. A very small droplet size of emulsion can provide an effective encapsulation for delivery system in the body. The formulation was carried out using low and high pressure homogenizer. The effects of palm oil esters:ricinoleic acid, lecithin, Tween 80, glycerol, and water on the droplet size as a response were studied. Under optimum formulation, the corresponding predicted response value for droplet size was 109.05 nm, excellent agreement with the actual value (109.12 nm) with residual standard error, 0.06%. Volume median diameter of nanoemulsion was 4.907 ± 0.067 μm. These results suggest that quercetin nanoemulsion in this study is ideal for pulmonary delivery.

Agathe Figarol has developed her expertise in nano-bio interactions since her MSc. thesis in Health and the Environment (Cranfield University, UK). Looking at the cellular impact of silica nanomaterials on keratinocytes, she was already starting to combine the different approaches of physical chemistry and biology relying on her technical background in biology engineering (Université de Technologie de Compiègne, France). She further enhanced her pluridisciplinarity along her PhD exploring the impacts on physico-chemical characteristics of carbon nanotubes on macrophages (Ecole Nationale Supérieure des Mines de St-Etienne, France). Her confirmed enthusiasm for the dynamic and state-of-the-art field of nanobiology led her, after a year of discovery of the industrial strategy on toxicology, to join a collaborative project on polymeric nanovectors (IPBS and IMRCP laboratories from the Université Paul Sabatier de Toulouse, France).

Statement of the Problem: The work presented here suggests a new approach in the critical development of polymeric nanovectors for photodynamic therapy (PDT) against cancer. Whereas hundreds of studies quickly jump forward from formation of self-assemblies to biological application without having a thorough examination of the vector solution, we suggest having a parallel assessment of formation/characterization of the nanovectors and their biological activity. This is possible by first conducting a careful physical chemistry characterization of the vectors by both batch techniques (light and neutron scattering, electron microscopy, atomic force microscopy) and Asymmetrical Flow Field-Flow Fractionation (AsFlFFF) coupled to adequate detectors (refractometry, light scattering). This enables us to fully characterize the vectors regarding purity, size and zeta potential. Methodology & Theoretical Orientation: Data on both polymeric micelles and polymersomes are presented here, using poly(ethyleneoxide-b--caprolactone), poly(ethyleneoxide-b-D,Llactide) and poly(ethyleneoxide-b-styrene). Self-assemblies exhibiting size range of 20-200 nm are presented and reveal the possible presence of different populations of nanovectors in some cases. Controlled mixtures of different nano-objects are also studied, as well as crosslinked systems. For each new vector, its ability to carry a photosensitizer (Pheophorbide a) for PDT is examined. The activity in PDT either in 2D and 3D cell culture is presented and compared on different batches, in link with the purity analysis. Here again, it becomes highly recommended to develop a critical approach considering in vitro analyses, since different efficiencies are clearly observed depending on the vectors and the 2D or 3D culture type.

Agrawal Satish has his expertise in formulation of novel, specially nano-drug delivery systems and their biomedical testing in animal models. He has completed his B.Pharm from Pune University, M.Pharm from BITS Pilani University, and currently pursing PhD from Central Drug Research Institute, Lucknow, India. He has also completed PGDBA (Operations) from Symbiosis centre for Distance Learning, Pune. He has published 9 papers in reputed journals and has strong passion for research in drug delivery systems.

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. However, there are many drawbacks associated with LPT that limits its therapeutic activity. In order to address the limitations associated with LPT, we have prepared its nanocrystals (LPT-NCs) those were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed investigation of LPT-HA-NCs showed the superior anticancer activity than its counterparts LPT-NCs and free LPT. LPT-HA-NCs were associated with increased cytotoxicity and the enhanced uptake in MDA-MB-231 cells due to active targeting to CD44 and EGFR receptors. It was also evident that the LPT-HA-NCs induced apoptosis is due to the Fas and mitochondrial membrane potential dependent pathway. The results of in-vitro studies were followed very well in the in-vivo studies. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs not only increased the residence time of LPT, but also targeted the tumor, reduced the tumor burden, and increased overall survival. Our findings clearly suggest that HA coated LPT-NCs formulation enhances the activity of LPT against triple negative breast cancer. It exhibited magnificent therapeutic outcome at low dose thus presenting a strategy to reduce dose administrations and minimize dose related toxicity.

Badis Bendjemil,University Badji Mokhtar,Algeria

Combustion synthesis in a self-catalytic propagation High Temperature Synthesis mode (SCHS) and arc discharge technic was used with the aim to synthesize 1D carbon nanostructures, by the sodium Azide NaN3 reduction of the Teflon PTFE (CF)n, in argon, at ambient pressure of 1 MPa. In the same time, several possible catalysts were tried, such as Fe(CO)5, Co(CO)5, Ni(CO)5 powders. Through the presence of NaF in the product, the deep reduction of PTFE is shown. In order to produce fullerenes and carbon nanotubes, On the other hand, we obtain nanocarbon reinforced iron nano-composites by nanocarbon encapsulated iron metal nanoparticles in nanocarbon coke were obtained in our samples with high yield, opening the process to new possible and nanobiotechnology applications as markers and therapy of cancer and in drug delivred by using of nanocarbon containers encapsulated by (ferromagnet is the heater of cancer tissue, markers and drugs). In oder hand the functionalized nanocarbon by magnetic hydroxipatite and cellular growth near nanocarbon for neural prosthetics is now in progress.

Mina Emamzadeh (BSc, MRes) is PhD student in cancer nanomedicine at UCL School of Pharmacy, London. Mina’s research is focused on the development of therapeutic nanoparticle for cancer therapy. In the present project, she develops radically new therapeutic protocols that combine lasers and gold nanoparticles to direct drugs at the diseased sites of the body in a specific manner without damaging healthy tissue. She also has experience in dendrimer-based nanomedicine.

The unique combination of optical and chemical properties of gold nanoparticles (GNPs) renders them an appealing nano-scale platform for cancer therapeutics. In this project we focused on the development of a new generation of theranostic GNPs for cancer treatment by the co-delivery of anti-cancer drugs in concert with confined laser induced photothermal tumor ablation. We anticipate that the combinatorial photo-chemotherapeutic protocol will exhibit significantly higher apoptotic cell rates without damaging the non-irradiated healthy tissue areas.Gold nanoshells (GNSs) were synthesized with the capability to carry and deliver gemcitabine and exert synergistic photo-chemo-therapeutic properties. A protein repellent thiol capped poly (ethylene glycol) methacrylate polymer, with molecular weight of 15000 g/mol, was synthesized by radical addition fragmentation (RAFT) polymerization and used as a particle stabilizing polymeric shield. Significant levels of stability enhancement were achieved allowing for the co-functionalization of GNSs with gemcitabine (GEM) for applications in assays and drug carrier systems. GNSs mediated strong photothermal effect owing to their strong surface plasmon absorption in the NIR region. This property was exploited for the controlled release of GEM using NIR light as the external photostimulus to trigger drug release. The drug loaded GNSs exhibited synergistic cytotoxicity against a model pancreatic cell line (MiaPaCa-2) owing to the concerted antitumor activity of GEM with the photothermal effect of the GNSs upon irradiation with the laser.

L. Nandhakumar is a Professor & Head, Sri Indu Institute of Pharmacy, Ibrahimpatnam, Hyderabad- 10, and INDIA. Researcher in studying the plant components for the treatment of diabetes in novel Nanotechnology, Also focusing on the antioxidant studies in treating diabetes

Statement of Problem: Basically flavonoids are naturally occurring phenolic compounds that are distributed in plants. They contain wide range of biological activity and lot of research has been carried out on their potential role in treating diabetes and other diseases. Most importantly the flavonoids and their related natural compounds are known to encompass antidiabetic potential, demonstrated in various animal models. Such beneficial flavonoids are less utilized on account of its deprived solubility, decreased bioavailability; first pass metabolism and intestinal degradation. However, flavonoids are capable of improving, stabilizing and long sustaining the insulin secretion, human islets and pancreatic cell respectively. Methodology & Theoretical orientation: In this article we propose, remarkable antidiabetic activity of flavonoids as well as few approaches on nanoparticulate systems in diabetes induced animal models. The proposed nanoparticulate system of flavonoids is projected to improve the solubility, bioavailability, by passing the first pass metabolism and decreasing susceptibility to intestinal environment as compared to pure flavonoid isolates. Conclusion and Significance: Further, this hypothesis exemplifies to enhance the efficacy of flavonoids in a novel way of antidiabetic treatment. 1. Designing of nanosized bioflavonoids using biodegradable polymeric nanoparticles by Plackett Burman method. International Current Pharmaceutical Journal. Vol 1, issue 1, Jan 2017. 2. Hypothesis on Novel Bioflavonoid Formulations towards Treating Diabetes Mellitus. American Journal of Pharmacy and Health Sciences. Volume 4, Issue 9, Sep 2016. 3. Stability studies of Eudragit loaded bioflavonoid nanoparticles for Antidiabetic and Antioxidant activity. International Journal of Pharmacy and Industrial research. Volume 6, Issue 2, Sep 2016. 4. Flavonoids insulinogenic action” may be “A promising alternative for diabetes” management. American Journal of Pharmatech Research. Volume 6, Issue 5, June 2016. 5. Analytical hierarchy process: A multi-criteria decision making approach for nanoparticles preparation method. International journal of pharmacy and Analytical research. Volume 3, Issue 4, Dec 2014.

Zi Xian Liao received her Ph.D. (2013) degree in National Tsing Hua University (NTHU), Taiwan. She currently serves as a assistant professor of Institute of Medical Science and Technology at National Sun Yat-sen University (NSYSU), Taiwan. Her main research interests focus on biomaterials applied for drug/gene delivery particularly genetically engineered protein, DNA and RNAi, continuously at controlled rates for prolonged of time.

Clinical virotherapy has been successfully approved for use in cancer treatment by the U.S. Food and Drug Administration; however, a number of improvements are still sought to more broadly develop virotherapy. A particular challenge is to administer viral therapy systemically and overcome limitations in intratumoral injection, especially for complex tumors within sensitive organs. To achieve this, however, a technique is required that delivers the virus to the tumor before the body’s natural self-defense eradicates the virus prematurely. Here we show that recombinant adeno-associated virus serotype 2 (AAV2) chemically conjugated with iron oxide nanoparticles (∼5 nm) has a remarkable ability to be remotely guided under a magnetic field. Transduction is achieved with microscale precision. Furthermore, a gene for production of the photosensitive protein KillerRed was introduced into the AAV2 genome to enable photodynamic therapy (PDT), or light-triggered virotherapy. In vivo experiments revealed that magnetic guidance of “ironized” AAV2-KillerRed injected by tail vein in conjunction with PDT significantly decreases the tumor growth via apoptosis. This proof-of-principle demonstrates guided and highly localized microscale, lighttriggered virotherapy.

Nina Filipczak is a Ph.D. student at Lipid and Liposomes Department (University of Wrocław). Her current research focuses on the use of liposomal nanomedicine for the effective treatment of melanoma cancer. She is also interested in other drug delivery systems, immunooncology and cancer biology

This work describes a novel targeted liposomal formulation of mitoxantrone, loaded by vitamin C gradient for remote drug loading, which also co-encapsulates anacardic acid in the liposome bilayer. The vitamin C gradient used for mitoxantrone encapsulation in this research was developed in our laboratory, and previously it showed promising results in terms of pharmacokinetics and tumor growth inhibition of liposomal epirubicin [1]. While the formulation was significantly effective on human melanoma, its efficacy could be further improved by active targeting [2]. Surface modifications with ligands specific to receptors which are over-expressed in cancers, or antibodies specific for tumor surface antigens, can enhance the accumulation of liposomes and their encapsulated drug in a tumor. Among these possible targets, cancer cells are known to overexpress transferrin (Tf) receptors many-fold compared to healthy cells [3] due to increased iron requirement. Hence, targeting the tumors with Tf-conjugated drug delivery systems represents a logical approach to drug delivery. The purpose of this study was to develop Tf-targeted delivery systems co-encapsulating anticancer drugs and anacardic acid, and to evaluate their efficacy in melanoma cells, grown in vitro in a 3D spheroid model. Tf-targeted liposomes were prepared by post-insertion of Tf-PEG conjugate into liposomes produced according to our previous method [2]. Melanoma cells generated spheroids with a distinct necrotic core along with proliferating cells in the spheroid periphery, partly mimicking in vivo tumors. Our results showed that the Tf-targeted liposomes were able to penetrate deeper layers of spheroids compared to non-targeted liposomal formulations, indicating a higher possibility of delivering drugs more efficiently into the tumor masses.

Paola Castaldo is the CEO of Fastissues srls and she also is a high school teacher of Applied Mathematics. She earned a PhD in Mathematics for Economic and Financial Applications and a PhD in Technology and Production Engineering. Her skills are the result of years of experience in simulation, evaluation, teaching and administration both in research and education institutions.

Statement of the Problem: As bone tissue engineering is concerned, a scaffold has to provide a suitable mechanical function in order to withstand loads and to transfer the stress to the hosting tissue. Polymer-based based composite scaffolds can be processed through the additive manufacturing approach (e.g. FDM) in order to design custom made scaffolds. The purpose of this study is to analyze the stress distribution into a 3D nanocomposite scaffold according to a compressive state of stress. Methodology & Theoretical Orientation: Cylindrical Polycaprolactone/nano-Hydroxyapatite 80/20w scaffolds were biomanufactured through a 3D plotter dispensing machine (Envisiontec GmbH, Gladbeck, Germany) at pressure of 8.5 bar and a temperature of about 120°C. Compression tests were carried out with an INSTRON 5566 at a rate of 1 mm/min. Finite element modelling (FEM) was carried out through the ANSYS software. The representative 3D scaffold design is shown in Figure 1A. The Young’s modulus and the Poisson’s ratio were set at 650MPa and 0.35, respectively. The mesh of a single unit of the cylindrical scaffold consisted of 397113 SOLID186 elements (Figure 1B). Findings: As the scaffold undergoes a compression load, the compressive stress is mainly transferred through the regions where the plotted fibers cross each other and through part of the round boundary. Moreover, a tensile state of stress is clearly evident on the regions of fibers close to the crossing points (Figure 1C). FEM simulations are in a good agreement with the experimental results as suggested by Figures 1D. Conclusion & Significance: FEM simulation in conjunction with experimental testing represent a very powerful tool to design custom made scaffolds.

Berwin Singh S.V is a Ph.D. student at the Chonbuk National University in South Korea working under the supervision of Prof. Dongwon Lee. He received his Masters in Bio Medical Science from the Bharathidhasan University, India, then He was trained in Bio Medical technology (M.Phil) at the Sri Chitra Instititute of Medical Science, India. His current research is focused on smart polymer synthesis-physiochemical characterization, developing and evaluation of nano-carriers in vitro and in vivo.

Statement of the Problem: Photodynamic therapy (PDT) is a treatment modality that employs an extrinsic photosensitive dye that could mediate a photochemical reaction involving conversion of molecular oxygen from triplet state to singlet in the presence of photons of suitable wavelength. However, penetration of the photons to the tumor interstitium is a major concern that limits PDT in majority of the biomedical application. At present, several researchers have developed “self-illuminating” PDT systems, in which photosensitizers are excited by chemiluminescent resonance energy transfer (CRET) or bioluminescent resonance energy transfer (BRET). In this work, we had demonstrated use of hydroxybenzyl alcohol-incorporating copolyoxalate peroxalate ester loaded protoporphyrin nanoselfassembly (CDNP) that could mediate chemiluminasencedynamic therapy (CDT). Methodology & Theoretical Orientation: CDNP react with HPOX to generate 1,2-dioxethanedione as an intermediate of high energy. Highly unstable 1,2-dioxethanedione rapidly decomposes and releases energy which could activate PPIX to generate 1O2 that ultimately kill the cancer cells: we termed this POCL dependent event as CDT. Findings: We successfully developed CDNP with average diameter of 200 nm. Morphological assessment, flow cytometric analysis, western blotting and confocal fluorescence micrographs indicates CDNP co-treatment with CA exhibited significant cytotoxicity in SW620 cells (human colorectal adenocarcinoma). Conclusion & Significance: we have validated that CDNP could induce 1O2 in the presence of H2O2 without any external photon to exert highly potent anticancer activity. This work provides for the first time, a proof of concept for laser-free PDT as a novel anticancer therapeutic system. We anticipate that CDT could provide solutions to the challenges in PDT and hold great potential as a promising cancer treatment modality.