2^nd International Conference and Exhibition on Nanomedicine and Drug Delivery May 21-23, 2018 Tokyo, Japan

Miriam Schiffer is especially interested in gene and cell therapy after myocardial infarction. Combining both therapies with Nanoparticles opens new options in order to enhance their effectiveness. She completed her apprenticeship as biological technician in the Grünenthal group (2012). Focused on molecular cell biology, she graduated as Master of Science (RWTH Aachen University) in 2016. Since then, she works as research assistant and PhD Student in the department of Cardiac Surgery at the University Hospital Bonn. Under supervision of Prof. Dr. Wilhelm Röll she writes her dissertation with the following title: Lentiviral gene transfer of the ischemic myocardium assisted by magnetic nanoparticles.

Besides heart failure, ventricular tachycardia (VT) is one of the most prevalent causes of death following myocardial infarction. Since cardiomyocytes are terminally differentiated cells, they are replaced predominantly by fibroblasts, which maximally proliferate on day 3 to 4 post infarction. Despite cardiac fibroblasts expressing the gap junction protein Connexin 43 (Cx43) on a basal level, propagation of the electrical conduction is reduced massively within the infarction area and VT can originate from re-entry mechanisms. Our goal is to enhance the conduction velocity within the scar by increasing the Cx43 expression in resident fibroblasts through direct intramyocardial lentiviral (LV) gene delivery or by intramyocardial transplantation of Cx43 overexpressing cardiac fibroblasts. Both the LV transduction efficiency and the engraftment of transplanted cells can be enhanced by the application of magnetic Nanoparticles (MNP) and magnetic fields. Besides the higher transduction efficiency, the application of MNP/magnet system enables a localized lentiviral transduction in vitro and in vivo. Our cooperation partners of the “Research Network Europe Japan” provided a PMAO coated magnetic particle labeled with TAMRA fluorochrome. This particle is characterized in vitro by a low toxicity (cell loss of 20 % at 25 pg / cell after 24 hours MNP treatment analyzed in MTT Assay) and high magnetic cell retention (80 % of cells after 24 hours incubation and 100 pg Fe /cell). In addition the used lentiviral (LV) constructs (rrl-CMV-Cx43-IRES-eGFP and rrlCMV-IRES-eGFP) complexed well with this MNP, since gene expression in fibroblasts was similar after overnight incubation without magnet application and following 30 minutes incubation under magnetic attraction. In conclusion, we could show that our target MNP is incorporated into fibroblasts resulting in low toxic effects but high magnetic cell retention. Additionally we were able to demonstrate a successfully complexation of MNP and LV, which allows faster and localized lentiviral cell transduction.

Esther Carls Has Her Primary Research Interest In Cardiovascular Diseases. She Has Completed Her Bachelor Degree In Life Sciences In 2011 And Her Master Degree In ‘Clinical Molecular Sciences’ In 2012 Focusing On Macrophage Cell Therapy In Atherosclerosis. Following This She Worked At The University Of Edinburgh On Macrophage Cell Therapy In Renal Ischemia. Since 2014 She Has Been Working At The University Hospital Bonn’s Dept. Of Cardiac Surgery On Cell And Gene Therapy In Myocardial Infarction. In 2017 She Started Work On Her Phd Thesis Under The Supervision Of Prof. Dr. Med. Wilhelm Röll.

After myocardial infarction, one of the major complications, besides a reduced ejection fraction (EF), is the occurrence of ventricular tachycardia (VT). The loss of cardiomyocytes in the infarction area is structurally compensated by their replacement with fibroblasts during scar formation. The massive loss of Cx43 expression within the infarct zone hampers electrical conduction and favors ventricular tachycardia (VT) by re-entry mechanisms. Therefore we hypothesized that intramyocardial transplantation of Cx43 expressing embryonic cardiac fibroblasts (eCF) following myocardial infarction could reduce post-infarct VT incidence. eCF were harvested on E13.5 and cultured for 7 days and transduced with either a Cx43-IRES-GFP or an IRES-GFP lentivirus (LV) construct in vitro. Subsequently they were loaded with fluorescently labelled, PMAO coated magnetic nanoparticles (MNP) overnight. Mice (female CD1, 10-12 wks.) underwent cryogenic induction of myocardial infarction and 200.000 cells were subsequently injected into the infarction area, either with or without application of a magnetic field. Functional analyses were performed 14 days post op by echocardiography and electrophysiological examination. Injected eCF were retained in the infarction area as shown by GFP expression of fibroblasts in the infarction area as well as the presence of the MNP. In the Cx43 transduced eCF injected mice an increased expression of Cx43 in fibroblasts could be observed. Functional examination revealed significantly increased anterior wall thickening (AWT) and improved arrhythmia resistance in mice injected with Cx43 expressing eCF (+Magnet, 25.0% VT incidence, n=8) compared to mice injected with GFP control virus (+Magnet, 77.7% VT incidence, n=9). However, there were no significant differences in global left ventricular function (fractional shortening) between groups. In conclusion, the transplantation of Cx43 expressing eCF protects against VT after myocardial infarction, but does not improve heart function.

Barbara Adinolfi Received The Master Degree In Pharmaceutical Chemistry And Technology In 2000 From The University Of Pisa, Italy. She Received The Phd In Pharmacotoxicological, Pharmacognostical Sciences And Pharmacological Biotechnologies In 2005 From The University Of Milan And The Specialization In Pharmacology In 2008 From The University Of Pisa. She Has Worked From 2000 Until 2013 At The Department Of Pharmacy, University Of Pisa. She Also Spent A Period (2009-2010) In The Department Of Biomedical Sciences, University Of Copenhagen. At Present She Is At The CNR Institute Of Applied Physics In Florence. Her Research Activity Is Focused On The Evaluation Of Anticancer Activity Of Natural And Synthetic Compounds, On The Evaluation Of The Role Of Specific Proteins As Putative Prognostic Markers In Cancer And On The Activity Of Nanoparticles As Intracellular Delivery Tools For Oligonucleotide Optical Switches By Confocal Microscopy.

Statement Of The Problem: The Development Of Effective Drug Delivery Systems Represents One Of The Main Goals In Nanomedicine. Data In Literature Demonstrate That, Depending On The Uptake Pathways, The Nanocarriers And Their Payloads Can Be Trafficked Into Different Organelles. In This Context, The Aim Of The Work Was To Evaluate: A) The Ability Of Polymethylmethacrylate Fluorescent Nanoparticles (PMMA-Nps) To Promote, In Human A549 Cancer Cells, The Internalization Of A Molecular Beacon (MB) Specific For Survivin Mrna As Theranostic Agent; B) The Involvement Of Endocytosis In The NP Uptake; C) The NP Fate At Different Times Of Cell Incubation To Verify Their Localization In Lysosomes; D) The MB Localization In Relation With The Endoplasmic Reticulum (ER) Where The Target Mrna Is Located. Methodology: The PMMA-NP Capability To Promote The MB Uptake By Endocytosis And The NP And MB Intracellular Localization Studies Were Realized By Confocal Microscopy Using Markers Of Endocytic Process And Organelles; The NP Fate Was Also Evaluated By Fluorescence Measurements. Findings: A) PMMA-Nps Promote The MB Uptake; B) Significant Increase Of The Number And The Mean Area Of Dextran Filling Endocytic Vesicles In The Presence Of Nps After Incubation Of 30'; C) Strong Co-Localization Of NP And Lysosome Tracker Fluorescence After 2-48 Hours Of Incubation (The Cell Culture Medium Fluorescence Decreases In The 24-72 Hour Window And Increases After 96 Hours); D) Co-Localization Of The MB Fluorescence With The ER-Marker Signal After 90' Of Incubation. Conclusion & Significance: These Data Highlight The Ability Of The PMMA-Nps To Promote The Survivin-MB Internalization And The Involvement Of Endocytotic Pathway In Their Uptake. These Results Demonstrate That The PMMA-Nps Are An Appropriate Delivery System Capable Of Being Eliminated By The Cells Involved In The Treatment; These Evidences Also Contribute To Consider The MB As An Effective Tool For The Intracellular Sensing.

Dr. Ming-Jun Tsai graduated from School of Medicine, Chung Shan Medical University and finished his PhD program on Cheng-Kung University. Dr. Ming-Jun Tsai is now the Chief of Department of Neurology, China Medical University-an Nan Hospital and the associate Professor of China Medical University, Taichung, Taiwan. Dr. Tsai focused on the research of drug delivery in clinical diseases. He has published more than 20 papers in drug delivery in clinical diseases, especially in neurologic diseases including stroke and parkinson’s diseases. Dr. Tsai also has extensive experience in international regulation of Medical Device and Drugs. Prior to join China Medical University, Taichung, Taiwan, Dr. Tsai served from 2007 through 2011 as Senior Reviewer of Pharmaceutical affair of DOH, which integrated into Taiwan Food and Drug Administration (Taiwan FDA) on 2009. Dr. Tsai has been signed to the US authority of medical device, CDRH of US FDA and Canada authority of medical device, Food and Drug branch, Health Canada for medical device regulation training. On behalf of DOH, Dr. Tsai also participated in WHO international pharmacovigilance program on 2008. On behalf of Taiwan Food and Drug Administration, Dr. Tsai has been invited to Drug Information Association and APEC as a speaker for regulation of Drugs and Medical Devices in Taiwan on 2009 and 2010, respectively.

Rosiglitazone (RSG), marketed as an antidiabetic drug, is a potent peroxisome-proliferator activated receptor-γ (PPAR-γ) agonist working on insulin-sensitizing and increase of glucose influx into adipose tissue and muscle. It has shown neuroprotective effect against ischemic stroke in recent clinical studies, whereas, severe side effect including cardiac toxicity restricted clinical use. RSG is.. The purpose of the study is to develop a better liposome formulation of RSG to enhanced CNS penetration and limited systemic side effect. Liposome is produced by thin layer method. With different ingredient of liposome, we try a better formula to change tissue distribution and penetration through blood brain barrier for neuroprotection effect against ischemic injury from stroke. The characterization of rosiglitazone liposome is produced by dynamic light scattering including particle size and zeta potential. Pharmacokinetic and bio-distribution is carried out on Wistar rats. We use high performance liquid chromatography with fluoresecnt detector to check blood concentration and drug encapsulation efficiency. We also tested the effect of rosiglitazone embedded in liposome for enhancing brain targeting and reduced systemic side effect in the rat animal models of ischemic stroke.

Konstantina Nadia Tzelepi Is A Phd Student At The Open University, UK Collaborating With The Pharmaceutical Company Midatech Pharma On Investigating The Mechanism Of Gold Nanoparticles Toxicity In Cancer Cells. She Graduated With A Bsc (Hons) In Biochemistry And A Master Of Research In Biosciences From Cardiff University.

Cancer Research Is Drawing Major Attention Of The Scientific Community. The High Death Rates, The Recurrence After Treatment And The Widespread Occurrence Suggests An Unmet Medical Need For Successful Therapies And Early Diagnosis. Nowadays, Most Of The Cancer Treatments Are Restricted To Surgery, Radiation And Chemotherapy. All Of These Methods Carry The Risk Of Damaging Healthy Surrounding Cells, Tissues And The Tumour Area. Gold Nanoparticles Are At The Forefront Of Biological And Biomedical Research Showing An Increased Promise In Targeted Cancer Therapy Due To Their Unique Physicochemical Properties. They Offer The Advantage Of Interaction With Biomolecules Both At The Cell Surface Level And Inside The Cell. This Interaction Is Highly Dependent On Their Ligand Composition. Because Of Their Ability To Cross Many Biophysical And Biological Barriers, They Are Engineered As Platforms For Targeted And Effective Drug Delivery And Imaging Labels. In Our Study, 2nm Aunps Surface Functionalised With A 50:50 Ratio Of A Thiolated Α-Galactose Derivative And A Thiol PEG Amine (Figure 1) Are Examined For Their Toxicity Towards Normal (Hacat) And Cancer (HSC-3) Human Skin Cell Lines In Vitro. Using This Very Simple Ligand Structure, We Demonstrate A Cancer Selective Toxicity That Depends Upon The Synthesis Duration Of The Aunp Due To Differences In Their Ligand Density. A Remarkable Adherence To Filopodia Cellular Structure Is Observed As Synthesis Time Of The Aunps Increases. Such Adherence Is Possibly Linked To Caspase 8 Activation On The Cell Surface And Triggering Of Death Cascades Events, Thus The Higher The Toxicity.

Tim Leaver is the Director of Product Management and Commercialization at Precision NanoSystems. With over ten years of experience developing automation and microfluidic products and solutions in life sciences fields, he has worked on problems ranging from drug delivery to single cell genomics. He studied at the University of British Columbia in the field of Engineering Physics

Liposomes are attractive drug delivery systems for formulating low solubility drugs. While several liposomal drugs are presently marketed, liposome production is commonly a multi-step processes that requires significant process development to scale up production through preclinical and clinical development. Here, we leverage the reproducible, continuous flow nature of a microfluidic platform to control the nanoprecipitation of liposomes, rapidly tune liposome size and drug loading, and reduce process development associated with increasing scale of production. Two liposome formulations of the hydrophobic photosensitizer verteporfin were produced as model systems and scaled up in batch volume by an order of magnitude. A process for liposome formation and simultaneous drug loading was initially developed at bench scale, on a system designed for rapid formulation optimization at volumes between 1 mL and 15mL. A Soy-PC/cholesterol/DSPE-PEG formulation was optimized by systematically varying the flow rate ratio between the aqueous and organic phases at the input of the microfluidic mixer, and their total follow rate. Optimized formulation parameters were also used to produce a DMPC/Egg-PG formulation the more closely resembles commercially available formulations. Both formulations were transferred directly to a larger system designed for producing pre-clinical batches between 10mL and 1000mL. As a consequence of conserved microfluidic geometry between the two systems, formulation conditions were replicated exactly. Hence, the physical characteristics and encapsulation efficiency were found to be identical between formulations produced on the two systems. This reduces the burden of process development commonly encountered when scaling up traditional liposome production methods.

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.

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.

Jia-You Fang is now a Professor in the Graduate Institute of Natural Products at Chang Gung University in Taiwan. In addition, he is an Adjunct Professor in the Graduate Institute of Health Industrial Technology, Chang Gung University of Science and Technology and Department of Anesthesiology, Chang Gung Memorial Hospital. Over the past 25 years, he and his team have made contributions to the understanding of drug delivery, pharmaceutics, pharmacokinetics, nanomedicine, and cosmetology. His contributions add up to 249 peer-review articles, more than 6000 citations and H index of 44.

Cilomilast is a phosphodiesterase 4 (PDE4) inhibitor for treating inflammatory lung diseases. This agent has a narrow therapeutic index with significant adverse effects on the nervous system. This study was conducted to entrap cilomilast into PEGylated phosphatidylcholine (PC)-rich niosomes (phosphatiosomes) to improve pulmonary delivery via the strong affinity to pulmonary surfactant film. Neutrophils were used as a cell model to test the anti-inflammatory activity of phosphatiosomes. In an in vivo approach, mice were given lipopolysaccharide (LPS) to produce acute lung injury (ALI). The surface charge in phosphatiosomes that influenced the anti-inflammatory potency is discussed in this study. Results: The average diameter of the phosphatiosomes was about 100 nm. The zeta potential of anionic and cationic nanovesicles was -35 and 32 mV, respectively. Cilomilast in both its free and nanocapsulated forms inhibited superoxide anion production but not elastase release in activated neutrophils. Cationic phosphatiosomes mitigated calcium mobilization far more effectively than the free drug. In vivo biodistribution evaluated by organ imaging demonstrated a two-fold ameliorated lung uptake after dye encapsulation into the phosphatiosomes. The lung/brain distribution ratio increased from 3 to 11 after nanocarrier loading. The intravenous nanocarriers deactivated the neutrophils in ALI, resulting in the elimination of hemorrhage and alveolar wall damage. Only cationic phosphatiosomes could significantly suppress IL-1β and TNF-α in the inflamed lung tissue. Conclusions: These results suggest that phosphatiosomes should further be investigated as a potential nanocarrier for the treatment of pulmonary inflammation.

Cationic lipids are very promising for gene delivery, as they have the advantages of being easy to prepare, no immunogenicity and low toxicity. Since the first cationic lipid—DOTMA (N-[1-(2, 3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride) was used for gene delivery, numerous cationic lipids with different structures have been synthesized and used for the delivery of nucleic acids into cells. Cationic lipids have three basic chemical functional domains: a hydrophilic headgroup, a hydrophobic domain, and a linker bond. The linker bond of cationic lipid was between the polar head group and the hydrophobic tail domain, whose nature could influence the stability and the biodegradability of liposomes. Cationic lipids containing carbamate linker have shown great interests as they are stable in the neutral pH condition but liable to acid-catalyzed hydrolysis under appropriate circumstances. We designed and synthesized a series of carbamate-linked lipids bearing quaternary ammonium headgroup and identical length of hydrocarbon chains for in vitro gene delivery. The chemical structure of carbamate-linked lipids was confirmed by IR, 1H NMR, 13C NMR, and ESI-MS. The liposomes formed from carbamate-linked lipids and helper lipids (Chol or DOPE) could effectively bind and condense plasmid DNA into complex with proper size and zeta-potentials. And, the transfection efficiency and cell viability of some of carbamate-linked lipids was superior or parallel to that of two commercial transfection agents, Lipofectamine2000 and DOTAP. Therefore, the carbamate-linked cationic lipid might be a promising gene carrier that has high transfection efficiency as well as low cytotoxicity, and could be considered as carrier for gene delivery in vivo.

Rakesh Bastola has completed his bachelor’s degree in Pharmaceutical Sciences (B. Pharm.) from Pokhara University, Nepal. He has been awarded with University Topper Medal by Nepal Pharmaceutical Association, Nepal and Dean’s List Award by Faculty of Science and Technology, Pokhara University. He is currently doing his M.S. in Pharmaceutics in Keimyung University, Republic of Korea under the scholarship program known as “Korean Government Scholarship Program.” He is working under the supervision and guidance of Prof. Sangkil Lee. He has published 1 paper in reputed journal.

High pressure homogenization including microfluidization and phase inversion are manufacturing methods used for preparing emulsions. But our study mainly focused on the development of o/w emulsions with simple self-emulsifying process that requires only stirring without the use of sophisticated equipments. Adjuvanticity of emulsions were assessed with Mycoplasma hypopneumoniae antigen. The ratio of Span® 80 and Cremophor® ELP was fixed at 7:13 and pseudo-ternary phase diagram was prepared to identify the self-emulsifying region. 3%, 5% and 10% squalene emulsions were prepared with deionized water. Furthermore, 0.01% (w/v) and 0.02% (w/v) carbomer solutions of C-971P NF and C-940 grades were also used to prepare emulsions. Altogether 15 emulsions were chosen and characterized by measuring particle size and zeta potential. Toxicity and immune response studies were done in BALB/c mice and blood samples of mice were tested for Mycoplasma hypopneumoniae-specific antibody titers. In our study, most of the emulsions exhibited droplet size in submicron size range and maintained throughout the period of 3 months. Majority of them maintained zeta potential values between -40mV to 0 mV. Emulsions could maintain their homogeneity upon gentle shaking. They showed no toxic effects and their immunogenic responses were good enough to compare with positive control-Montanide ISATM 201. Acknowledgements: This research was supported by Technology Development Program (Project No. 316093-2 and Project No. 316094-2) for Bio-industry, Ministry for Agriculture, Food and Rural Affairs, Republic of Korea.

Gyubin Noh completed his Bachelor course from Keimyung University, College of Pharmacy, Daegu, Republic of Korea on February, 2016. He started MS-PhD course at College of Pharmacy, Keimyung University, Daegu, Republic of Korea from September 2016 to till date. He is now studying in 3rd semester. He is interested on transdermal drug delivery, biopharmaceutical delivery, microneedle etc

The objective of this work was to evaluate the combined effect of microneedle and iontophoresis on transdermal recombinant human growth hormone(rhGH) delivery. rhGH was used as a model macromolecule. Methylene blue staining, stereomicroscope and SEM imaging were used to characterize the microchannels. The effect of molecular charge on transdermal delivery was evaluated by permeation study in two different buffer – PBS (pH 7.4) and citrate (pH 4.0). Since hGH is negatively charged at pH 7.4 and positively charged at pH 4.0, cathodal and anodal iontophoresis was applied respectively. And the effect of current density was evaluated in three different electrical densities of 0.125, 0.25 and 0.5mA/cm2. With the optimized iontophoresis protocol, permeation studies were performed to evaluate combination effect of iontophoretic delivery through microchannels under three different settings : (a) iontophoresis alone, (b) microneedle pretreatment, (c) microneedle pretreatment with iontophoresis. The cumulative amount permeated and flux in all experiments reached a plateau in 1 hour. Anodal iontophoresis in citrate buffer showed about 10-fold higher flux of rhGH compared to cathodal iontophoresis in PBS. Also anodal iontophoresis with current density of 0.5mA/cm2 showed the 2.32 and 1.11-fold higher flux compared to 0.125 and 0.25mA/cm2 respectively. And compared to microneedle pretreatment and optimized iontophoresis alone, the combination of iontophoresis with microneedle showed 5.82 and 6.33-fold higher flux respectively. The result suggrest that anodal iontophoresis with higher current density enhance permeation of macromolecule through microchannels created by microneedles. In conclusion, combination of iontophoresis and microneedle is potential strategy for enhancing transdermal delivery of macromolecule..

Rajesh Singh Jadon is pursuing PhD in Pharmaceutical Sciences from Jiwaji University, Gwalior, India. Currently working on Development and evaluation of Nanocarriers for targeted delivery of bioactives. He has authored more than 15 Research and review articles and two books related to drug delivery systems. He is also a member of various professional bodies like controlled release society, Indian Immunology society, APTI, Association of registered pharmacists. He has around 12 years of experience in research, evaluation, teaching and administration in educational institutions.

More than 10 million patients are diagnosed with new cases of cancer every year and approximately 30 million new cases of cancer will have been recorded by 2030. While cytotoxic chemotherapeutic agents such as Docetaxel (DTX) and doxorubicin (DOX) efficiently kill cancer cells, they cannot differentiate cancer cells from normal cells. This lack of selectivity leads to unwanted systemic toxicity when patients are exposed to the cytotoxic agents. Improving the selectivity of anticancer drug delivery to cancer cells and the tumor microenvironment while sparing normal cells and tissues is a major challenge in the effective treatment of cancers of various tissues and organs. Marked differences are found in cancer cells and tissues in terms of biochemical, molecular and physiological features when compared with normal cells and tissues such as differences in redox status, pH levels, expression of certain cell membrane receptors, the leakiness of tumor tissues and the tumor vasculature. Therefore In this study, we exploit some of these differences cancer stands out as a disease likely to benefit from targeted drug delivery approaches. In this study we formulate and developed Surface decorated Lipid polymer hybrid Nanoparticles of Docetaxel for targeted delivery to breast cancer. Fu-LPHNPs were prepared using the single step nanoprecipitation method. Fu-LPHNPs comprised of poly(D, L-lactide-coglycolide) (PLGA) core, a soybean lecithin monolayer and (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-carboxy(polyethylene glycol)2000-Fucose) (DSPE-PEG2k-Fu) targeting ligand. For LPHNPs (non-targeting control), DSPE-PEG2k-FOL was replaced by DSPE-PEG2k. Fu-LPHNPs exhibited good monodispersity, excellent size, stability and a well-defined core-shell structure. Flow cytometry, confocal image and MTT assays revealed that Fu-LPHNPs further enhanced cell uptake via lectin receptors mediated endocytosis and resulted in higher cytotoxicity against Human breast adenocarcinoma cells (MCF-7) than non-targeted controls (LPHNPs).

Santosh Bashyal has completed his Bachelor in Pharmaceutical Sciences from Pokhara University, School of Health and Allied Sciences, Lekhnath, Kaski, Nepal on January, 2014. He is the registered pharmacist of Nepal (G 1512). He started integrated MS-PhD at College of Pharmacy, Keimyung University, Daegu, Korea from March 2015 to till date. Currently, he is studying in 6th semester. He has published two research review articles as the main author and another review article as a co-author. He is interested on drug delivery systems, buccal drug delivery, various non-invasive routes, nanocarriers, liposomes, iontophoretic drug delivery, biopharmaceuticals delivery, cell penetrating peptides (CPPs) etc.

The main aim of this study was to investigate the potential of various elastic liposomes containing different derivatives of cholic acid to improve permeation of insulin across in vitro buccal cell layers. Elastic liposome containing soya lecithin and bile salt edge activators (sodium cholate (SC), sodium deoxycholate (SDC), sodium taurocholate (STC), sodium glycocholate (SGC), sodium deoxyglycocholate (SDGC) or sodium deoxytaurocholate (SDTC)) were fabricated by thin film hydration method. The prepared liposomes were characterized and performed in vitro permeation studies. The cell viability (MTT assay) was done to find out the safe concentration for permeation studies across TR146 cell layers. The FITC-insulin-loaded elastic liposomes were used to evaluate the quantitative and qualitative cellular uptake studies. The prepared elastic liposomes were with a particle size and zeta potential of approximately, 150-160 nm and -40 to -50 mV, respectively. After 8 hours, the steady state flux, permeability coefficient and enhancement ratio were calculated from the linear part of the permeation curve. Compared to insulin solution, the SDGC-lipo significantly improved the permeation of insulin across the TR146 cell layers, with a 5.2-fold. Moreover, SC-lipo and SDTC-lipo enhanced the permeation of insulin with a 3.2 and 3.1-fold, respectively than as compared with insulin solution. These results were further supported by quantitative and qualitative cellular uptake studies that were performed with fluorescence-activated cell sorting (FACS) analysis and confocal microscopy, respectively. Thus, this findings revealed that the majority of insulin were permeated through transcellular route and can efficiently enhance the permeation of insulin across buccal cell layers.

YU Ligang has completed his master’s degree (organic chemistry) from East China Normal University. He is currently a graduate student (PhD Biomedical Sciences) in City University of Hong Kong.

Photodynamic therapy (PDT) is a novel therapeutic modality for the treatment of cancerous and non-cancerous diseases. However, the low selectivity of photosensitizers between normal and tumor tissues severely limits the clinical application of PDT. Zinc phthalocyanines based photosensitizers are promising candidates for PDT. To improve the biocompatibility and tumor selectivity, we employ an epidermal growth factor receptors (EGFRs) binding peptide (named GE11, a 12-amino-acid sequence) as a tumor directing vector for the delivery of zinc phthalocyanine. The GE11 conjugated zinc phthalocyanine (Pc-GE11) was easily prepared via solid phase synthesis based on our previous reported 1,4-bis(triethylene glycol)-substituted zinc phthalocyanine, which is a more efficient singlet oxygen generator. The photophysical properties, cellular uptake, in vitro toxicity and in vivo biodistribution of Pc-GE11 have been evaluated. The uptake of Pc-GE11 in A431 cells (high EGFRs expression) was higher than that in MCF7 cells (low EGFRs expression). Competitive assay also showed that free GE11 pretreatment inhibited the uptake of Pc-GE11. Besides, Pc-GE11 exhibited exclusive light-activated toxicity towards A431 cells. Furthermore, intravenous administration of Pc-GE11 showed the photosensitizer mainly accumulated in tumor and liver tissue in A431 tumor bearing mice. The in vivo PDT effect of Pc-GE11 is under evaluation currently. As such, Pc-GE11 is a promising EGFRs-targeted PDT agent.

TaeKwang Keum has completed his Bachelor in Pharmaceutical Sciences from Keimyung University, Daegu, Korea on February, 2015. He started integrated MS-PhD at College of Pharmacy, Keimyung University, Daegu, Korea from September 2016 to till date. Currently, he is studying in 3th semester. He is interested on drug delivery systems, buccal drug delivery, various non-invasive routes, nanocarriers, liposomes, biopharmaceuticals delivery, cell penetrating peptides (CPPs) etc

The aim of the present study is to investigate the permeation effect of penetratin for salmon calcitonin through porcine buccal tissue and compare with that of penetratin-conjugated liposome. Salmon Calcitonin was used as model peptide drug and L-Penetratin(RQIKIWFQNRRMKWKK) was chosen as cell penetrating peptide. Molar mixing ratio between sCT and penetratin of simple mixture formulations was from 1:0.1 to 1:2. Liposomes were prepared by thin-film hydration method using L-α-Lecithin, Tween80 and MPB-PE(N-[4 (pmaleimidophenyl)butyryl]-phosphatidylethanolamine) a synthetic phospholipid for penetratin-conjugated liposomes with the fixed molar ratio of 89:10:1 and 88:10:2. To react MPB-PE with Cys-penetratin, Cys-penetratin was mixed and reacted with MPB-PE anchored onto liposomes for 12 hr under 4℃ with stirring. Particle size and zeta potential were measured and transbuccal permeation experiment was performed for 8 hr using Franz diffusion cells. In this study, penetratin enhanced the transbuccal permeation of sCT compared to sCT control formulation, and 1:1 mixture showed 93.7-folds higher apparent flux(Js,app) than control, and 1:1 ratio was thought as optimal concentration. The particle size of penetratin-conjugated liposomes was 140.5±3.4 nm and 155.8±4.2 nm respectively. Zeta potential of penetratin-conjugated liposomes was +29.6±3.6mV and 35mV higher than Control liposomes. The apparent flux of penetratin-conjugated liposomes(ratio of 89:10:1) is 2.46-folds higher than Control and 75.9-folds higher than control. We found the optimal concentration of Penetratin and penetratin-conjugated liposomes for sCT buccal tissue permeation. By conjugating Penetratin onto the liposomal surface, the permeation property of of liposome might be governed by Penetratin. Understanding of full permeation mechanism might be possible after performing further study using different type of CPPs. (This work was supported by NRF-2016R1D1A1B01015369)

Suchi Thakur has her expertise in the formulation and evaluation of nano Pharmaceuticals. The nano delivery system in Pharmaceutical was expanded by her in the form of transferosomes, liposomes, niosomes at nano and micro level. She has contributed her knowledge in many research projects and giving her best at institutes by teaching which creates a new pathway in improving healthcare in pharmaceutical level. Her recent research work is going on the Microfluidic technique, formulations of nanoparticulate or nano medicine at lab on chip method. This is a novel expansion in bionanomaterial synthesis which in future give a great response and have a different way of focusing in prospect, which will lead to a benchmark in pharmaceutical companies.

The investigation indicates, Non ionic surfactant based vesicular system to enhance residence time of Gancyclovir (GCV) in tear film at ocular site. Even the Niosomes elastic vesicular system can penetrate the posterior eye segment as compare to the conventional Liposomes. The formulation consists of GCV embedded in chitosan, cholesterol (Chol), sorbitanmonostearate (Span 60). Methanol, chloroform was used as organic solvent to dissolve lipid ingredients. Classical mechanical dispersion method by rotary vacuum evaporator was used to formulate niosomal vesicles, which are then characterized for safety, efficacy and stability. Niosomes with average diameter of 436.70±1.3 nm were prepared. Different batches (C1NG5 to C5NG5) were prepared using varying concentration of chitosan (0.1 to 0.5 %) while taking chol and span 60 at constant molar ratio of 2:1 (w/w). The batches C1NG4 shows the desired release of the GCV as compared to C1NG5. No eye irritancy was observed with C3NG4-C4NG5 batches and as compare to available marketed solution of GCV it has higher residence time at ophthalmic site. The results of the present study indicate that ophthalmic noisome of GCV with chitosan was developed; overcoming the problem related to the eye drop therapy because GCV is having low bioavailability in current study with effective mucoadhesive characteristics (p<0.05) we gain higher transcorneal permeability with no sign of irritation, swelling, and redness to conjunctiva, iris and cornea of albino rabbits (p<0.05)

In current scenario the biosynthesis of metallic nanoparticles has been attracted. In the present study, Aegle marmelos L. leaf extract was selected as a reducing agent to produce silver nanoparticles (AgNPs) by a green method with the endeavour of care for heptotoxicity in rats. The produced nanoparticles were characterized by UV–Vis analysis, Zeta sizer and Zeta potential, Scanning electron microscope (SEM), Fourier-transform infrared spectroscopy FTIR, and X-ray diffraction analyses. Healthy wistar rats (180±10 g) were administrated with dose of CCl4 (0.15 ml/kg, i.p.) for 21 days. Intoxicated animals were treated with green synthesized AgNPs at different dose at 150 µg/kg for five days. Liver as well as blood samples were collected for biochemical and molecular assays. Administration of green synthesized AgNPs transformed a variety of biochemical parameters, including serum transaminases (AST & ALT), hepatic lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalyse (CAT), serum albumin, serum lactate dehydrogenase (LDH), bilirubin, serum alkaline phosphatase (SALP), urea and uric acid which were refurbish towards normal by doses of Aegle marmelos mediated AgNPs, which was also supported by histopathological and molecular studies (COMET assay). Thus the study revealed Aegle marmelos extort of leaf as a potential reducing agent in addition to the usage of Aegle marmelos mediated AgNPs in the field of drug design.