Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 13th International Conference and Exhibition on Nanomedicine and Pharmaceutical Nanotechnology Rome, Italy.

Day 2 :

Keynote Forum

A J Mixson

University of Maryland School of Medicine, USA

Keynote: Hydrogen bonding enhances stability of HK nanoplexes

Time : 09:00-09:30

Conference Series NanoMed 2017 International Conference Keynote Speaker A J Mixson photo
Biography:

A J Mixson has been working since 1994 in the Pathology Department at the University of Maryland School of Medicine with an initial focus on non-viral delivery of anti-angiogenic “nucleic acids” (plasmids/siRNA/DNAzymes) with liposomes utilizing in vitro or in vivo model systems. Our current research has expanded to developing novel peptides as nucleic acid carriers and as antifungal agents. He has been awarded several US and European patents on gene therapy and anti-angiogenesis. During the last 12 years, our laboratory developed histidine-rich peptides as carriers of nucleic acids. We are particularly interested in the mechanisms that govern the stability and dissociation of histidine-lysine polyplexes. 

Abstract:

Statement of the Problem: Our laboratory has focused on developing histidine and lysine (HK) peptide carriers with varied complexity to deliver siRNA and plasmids in vitro and in vivo. Positively-charged lysines bind and protect DNA, partially neutralizing its charge, whereas histidines bind DNA, buffer endosomal pH and thus presumably aid in release of nucleic acids from endosomes. In addtion to these roles of HK, preliminary data indicate that non-ionic interactions between HK peptides and nucleic acids are essential.

Methods: After synthesizing branched peptides that contained varying amounts of histidines, we determined the influence of serum on the stability and gene silencing activity of these peptides in complex with siRNA. The thermodynamic profiles of siRNA binding to peptides with different histidine and lysine contents were then analyzed by isothermal titration calorimetry (ITC). To explore the presence of histidine-mediated hydrogen bonds, protonation of free and siRNA bound imidazoles was characterized using heteronuclear single quantum coherence (HSQC) NMR at pH 7.3 and 5.0.

Findings: A 4-branched HK peptide siRNA nanoplex maintained silencing activity even with prolonged pre-incubation with serum. In marked contrast, siRNA in complex with 4-branched NK4b, in which histidines were substituted with asparagines, showed a marked decreased in silencing activity. To explore whether histidine forms non-covalent bonds with nucleic acids, we compared the thermodynamic properties of HK with other lysine-analogues. While polylysine with siRNA resulted in an endothermic reaction, branched and linear HK peptides exhibited an exothermic reaction, indicating that non-ionic bond formation between histidines with siRNA. Moreover, the peak of Nd1- protonated tautomers of imidazole shifted downfield by 0.5 to 1.0 ppm with addition of siRNA, providing direct evidence that uncharged histidines formed hydrogen bonds.

Conclusions: These results establish that histidine-rich peptides form hydrogen bonds with siRNA, thereby enhancing the stability and biological activity of the nanoplex. 

Keynote Forum

Igor Chourpa

Université Francois Rabelais de Tours, France

Keynote: Pharmaceutical development of injectable nanomedicine targeting breast cancer

Time : 09:30-10:00

Conference Series NanoMed 2017 International Conference Keynote Speaker Igor Chourpa photo
Biography:

Igor Chourpa is Director of Analytical Chemistry Department at the Faculty of Pharmacy of the University François Rabelais of Tours, France, and Head of the research group “Nanomedicine & Nanoprobes” EA6295. This group develops nanomedicines for anticancer theranosis, i.e. diagnosis by medical imaging and therapy by delivery of chemotherapy or siRNA. His particular expertise domain is optical microspectroscopy (Raman, surface-enhanced Raman and fluorescence) and spectral imaging. He has authored 62 publications in peer-reviewed journals. He is member of Editorial Boards of J. Anal. Meth. Chem. (Hindawi) and Int. J. of Nanopart. Nanotechnol. (Helics). 

Abstract:

Anti-cancer theranosis (therapy and diagnosis) using nanomedicine is a promising perspective, related to a possibility to combine several diagnostic and therapeutic functions in order to potentiate them. Superparamagnetic iron oxides (SPIONs) are often used as nanomedicine platforms due to the possibility to stimulate their intratumoral staining and drug delivery with help of a magnetic field as well as to contrast tumors on magnetic resonance imaging (MRI). In order to inject SPIONs intravenously, their biocompatibility and efficiency has to be improved by surface coating with neutral biocompatible polymers like polethylene glycol (PEG) functionalized with molecular cancer targeting ligands like peptides and antibody fragments. We are developing PEGylated and bio-functionnalized injectable nanovectors based on PEGylated SPIONs. Their polymeric shell is covalently coupled with membranotropic cell-penetrating peptides gH625 and/or with scFv fragments of antibody trastuzumab which binds specifically to membranes of HER2 positive breast cancers. The nanosystems can thus act as vectors of chemotherapeutic drugs of anticancer-active siRNA. The pharmaceutical development strategy we apply includes not only a rational design of the nanosystems but also step-by-step optimization of their structure in order to reach the better biocompatibility/bioactivity. For each nanoform, tens of independent batches were generated and their physico-chemical characteristics (size and zeta potential, chemical composition and structure) were established. Prior to in vivo essay on breast cancer xenografts in mice, the nanoforms interaction with cancer cells has been studied in vitro, on various cancer cell lines, overexpressing or not cancer-specific receptors. Comparison of biological behavior of the ligand free vs. ligand carrying PEGylated nanovectors allowed us to demonstrate that the moderate presence of ligands was not able to affect the nanomedicine forms size and zeta potential. Nevertheless, the bio-ligands enhanced the nanomedicine-cell interactions, both quantitatively (intracellular accumulation) and qualitatively (internalization, subcellular distribution and cargo delivery/transfection). 

Keynote Forum

Anne Grobler

North-West University, South Africa

Keynote: The use of nano- and micro-delivery systems in the pharmaceutical space: Gold and beyond

Time : 10:00-10:30

Conference Series NanoMed 2017 International Conference Keynote Speaker Anne Grobler  photo
Biography:

Anne Grobler is the Director of the National Platform Preclinical Drug Development in South Africa, a joint initiative between the state and the academic sector. She has a PhD in Pharmaceutics from the North-West University and MSc in Medical Biochemistry from the University of Stellenbosch, South Africa. She has published more than 40 papers in reputed journals and is the Inventor of 5 patents granted in various countries. She has received a number of awards, including the BHP Billiton awards for her contribution to innovation

Abstract:

Gold nanoparticles (AuNPs) have shown great potential for use in nanomedicine and nanotechnologies due to their ease of synthesis and functionalization. However, their apparent biocompatibility and biodistribution is still a matter of debate due to the lack of clear safety data. To investigate the biodistribution of AuNPs, monodisperse 14nm dual radiolabeled [14C]citrate coated [198Au]AuNPs were synthesized and their physico-chemical characteristics compared to those of non-radiolabeled AuNPs synthesized by the same method. The dual radiolabeled AuNPs were administered to rats by oral or intravenous routes. After 24 h the amounts of Au core and citrate surface coating were quantified using gamma spectroscopy for 198Au and liquid scintillation for the 14C. The Au core and citrate surface coating had different biodistribution profiles in the organs/tissues analyzed and no oral absorption was observed. We conclude that the different components of the AuNPs system, in this case the Au core and citrate surface coating, did not remain intact resulting in the different distribution profiles observed. These results will be compared with those obtained with other organic-based drug delivery systems, such as the Pheroid® delivery system, where both the carrier and the active ingredient were also radiolabeled. A better understanding of the biodistribution profiles of surface attachments or cargo of delivery vehicles in relation to the carrier itself is required to successfully use the various organic and inorganic systems in drug delivery. 

Break: Networking & Refreshments Break 10:30-10:45 @ Foyer
  • Nanomedicines and Biomedical Applications | Pharmaceutical Nanotechnology | Nanomedicine and Drug Delivery | Novel Drug Delivery Technology | Nanotechnology for Targeted Drug Delivery | Nano Pharmaceuticals
Location: OLIMPICA 4
Speaker

Chair

Jonghwi Lee

Chung-Ang University, South Korea

Speaker

Co-Chair

Konstantinos Avgoustakis

University of Patras, Greece

Session Introduction

Jonghwi Lee

Chung-Ang University, South Korea

Title: Bio-inspired, microchanneled materials prepared by crystallization of solvents

Time : 10:45-11:10

Speaker
Biography:

Jonghwi Lee obtained his PhD degree in University of Michigan, Ann Arbor and worked for Merck Research Laboratories as a Senior Researcher after his Postdoctoral training at the University of Minnesota. He has won prizes from The Polymer Society of Korea (Best Paper Award), Korean Society of Industrial Engineering Chemistry (Contribution Recognition Award, Best Paper Award, Best Industry Collaboration Award), and Chung-Ang University (Excellence in Achievement Award, Bae Young Soo Award). He has published more than 150 research papers, and currently a Vice Editor of Journal of Industrial and Engineering Chemistry (IF = 4.179) and Macromolecular Research

Abstract:

Microporous polymeric materials in nature have well-controlled structures of skeletal walls and pores for their functions. The structures of man-made microporous polymers are commonly limited to isolated porous architecture, although they have continually been developed for the critical roles in various industries. The directional melt crystallization of solvent, a relatively new versatile preparation method to produce aligned pores in the forms of 3D patterns, has produced porous structures of Voronoi and honeycomb-like architecture morphology. By applying this technique to polymers, we have produced various materials having ordered microchannels. Crystallization rate and direction have been carefully controlled in a home-made apparatus to prepare defect-free materials having well-ordered through-thickness microchannels. From polymer solutions or dispersions, solutes become skeletal portion and crystallized solvents become pores after sublimation. The free-standing membranes of 60-90 vol% through-thickness porosity could be prepared without having internal microcracks. With the support of nanotemplates, nanospheres, nanorods, and nanomembranes could be prepared too. Controlling pore morphology by directional freezing offers a versatile route to prepare unique porous polymer and composites for future biomedical, electronics and environmental applications. 

Konstantinos Avgoustakis

University of Patras, Greece

Title: Multifunctional magnetic nanocarriers of anticancer drugs

Time : 11:10-11:35

Speaker
Biography:

Konstantinos Avgoustakis obtained his Diploma in Pharmacy from Aristotle University of Thessaloniki, Greece in 1985 and a PhD degree in Pharmaceutical Technology from King’s College, University of London, UK. Since 1994, he has joined the Department of Pharmacy in University of Patras (Greece), where he teaches subjects related to Pharmaceutics and Drug Delivery and since 2015 he has joined Biomedical Research Foundation of Athens Academy as Collaborating Researcher. His research interests lie on the controlled, targeted therapeutics delivery using engineered nanoparticles. He is the author of 60 articles in peer-reviewed journals and 1 article in Biomaterials Encyclopedia. He is also the author (inventor) of 1 European patent. His published research has received over 2000 citations with an h-index of 23. He is an Assistant Editor of the scientific journal Current Nanoscience. He has participated in several research programs in collaboration with academic and industrial organizations (in 7 as coordinator).

Abstract:

Magnetic nanoparticles have been intensively investigated for the selective delivery of anticancer agents. Magnetic drug nanocarriers provide further advantages as they concomitantly allow for tissue imaging through magnetic resonance imaging and can induce cell-destructive hyperthermia in tumor by application of external alternating magnetic fields. We have been investigated the application of hybrid organic/inorganic magnetic nanoparticles for a more selective delivery of potent anticancer agents to tumors. In this context, we developed recently pH-responsive magnetic nanocarriers based on the graft-copolymer of poly (methacrylic acid)-g-poly(ethyleneglycol methacrylate) for the controlled delivery of cisplatin. Enhanced in vivo anticancer therapeutic efficacy and reduced toxicity was recorded for these cisplatin nanocarriers in comparison to the free drug cisplatin, particularly when a magnetic field gradient was applied at the tumor site. A problem frequently encountered with drug nanocarriers is their low level of uptake by tumor cells. In order to overcome this problem, we have developed poly(lactide)-poly(ethyleneglycol) magnetic nanocapsules functionalized with a cell penetrating TAT peptide and loaded them with paclitaxel. The conjugation of the TAT peptide on the surface of the nanocapsules resulted to highly increased uptake of nanocapsules by A549 cancer cells and to a profound improvement of the cytotoxicity of the paclitaxel-loaded nanocapsules against the cancer cells. In order to increase magnetic responsiveness, we developed colloidal clusters of iron oxide nanocrystals (MIONs), particularly in the condensed pattern (co-CNCs). These MION-based co-CNCs were characterized by high magnetization and high relaxivities combined with remarkable colloidal stability and drug-loading properties. Hypoxia develops in solid tumors, which leads to the development of resistance of tumor cells to radiotherapy and chemotherapy. We are working on magnetic nanocarriers for the targeted (selective) delivery of sodium-glucose transporter protein inhibitors to tumors. This nanomedicine combined with radiotherapy or chemotherapy would represent an effective treatment of hypoxic tumors.

Speaker
Biography:

Khaled Greish graduated from the Faculty of Medicine, Suez Canal University, Egypt in 1992. He received his Master’s degree in Clinical Oncology in 1997. From 1999 to early 2008, he joined the lab of Professor Hiroshi Maeda, a world leader in the field of Anticancer Nanomedicine. Along with Professor Maeda, he developed an affordable platform nanotechnology micellar system for targeting anticancer drugs to solid tumors. In 2008, he moved to The University of Utah, as Research Assistant Professor. He joined Otago University in 2011, and currently Associate Professor at Arabian Gulf University, Bahrain. His areas of interest span the formulation and characterization of different advanced drug delivery systems, anticancer drug discovery/development, tumor vascular biology and animal tumor models. He was awarded the CRS Postdoctoral Achievement award in 2008 and, in 2010 he was elected as member of the CRS College of Fellows

Abstract:

The oral route is the most preferred mode of administration among patients, due to its non-invasive nature. Oral administration of therapeutics can improve the patient`s quality of life, reduce costs associated with hospitalization and avoid complications associated with intravenous injections. The primary barrier to clinical application of an oral therapeutic, is poor oral bioavailability, a result of the combination of low water solubility, low pH stability, poor mucosal penetration, extensive first pass metabolism, and P-glycoprotein (P-gp) efflux and enzymatic degradation. Nanocarriers present a unique opportunity to overcome these barriers due to their design flexibility, surface functionality, and ability to deliver a wide range of therapeutics. Nanocarrier systems can enhance the solubility of the bioactive, protect them from enzymatic degradation and allow incorporation of the appropriate surface functionalization to favor uptake through the intestinal epithelium. Additionally, nanocarriers can prevent the direct contact of the bioactive agent with the cells of gastrointestinal (GI) tract. Nanocarriers can thus reduce the toxicity, prolong the circulatory half-life of the bioactives and accommodate targeting moieties to enhance further their prospects as site specific delivery systems. In this presentation, we will discuss our work utilizing Styrene Maleic Acid (SMA) nanomicelles for oral drug delivery through two case studies. The first example involves the use of oral paclitaxel nanomiceller formulation for treatment of colon cancer. The second case will discuss the successful use of oral nanoformulation of the selective estrogen receptor modulator (raloxifene) for treatment of inflammatory bowel disease (IBD).

Katja Bettina Ferenz

University of Duisburg-Essen, Germany

Title: Perfluorodecalin-filled albumin nanocapsules as artificial oxygen carriers

Time : 12:00-12:25

Speaker
Biography:

Katja Bettina Ferenz has completed her PhD in Pharmaceutical Chemistry from the “Westfälische-Wilhelms-University Münster” in Germany. Since 2011, she leads her own research group, Development of Artificial Oxygen Carriers at the University of Duisburg-Essen, University Hospital Essen, Institute of Physiological Chemistry, Essen, Germany. She has published 14 papers in reputed journals and participates in the professional training of physicians specialized in transfusion-medicine with lectures on actual developments in the field of artificial oxygen carriers. Her research interests are artificial oxygen carriers, micro- and nanoparticles, nanomedicine, perfluorocarbons, drug delivery and biomaterials

Abstract:

Despite long lasting efforts, at present a harmless, effective artificial oxygen carrier is missing for clinical use both in Europe and USA. To bypass this, bottleneck albumin-derived perfluorocarbon-based nanocapsules (nanocapsules) were designed as a novel artificial oxygen carrier. Most importantly, nanocapsules do not contain any chemical emulsifier. Nanocapsules are synthesized in different size ranges (Ø 100-1500 nm) by using either ultrasonics or a microfluidizer apparatus. Physical assessment of size (DLS, REM/LSM), oxygen transport capacity or the charging of erythrocytes is performed. In different animal models of the rat (topload/ normovolemic hemodilution), physiological parameters (e.g. breathing, blood pressure), blood gases, electrolytes and signs of tissue impairment in plasma (e.g. ASAT, LDH) are monitored. Microcirculation of the liver (IVM) and intravascular half-life of nanocapsules and their multiple loading with O2 are measured (NMR). Successful in-vitro experiments concerning the oxygen transport capacity of the nanocapsules (oxygen supply of yeast cells, oxygenation of desoxy-Hb inside erythrocytes) and the proof of bio-functionality in the isolated organ (Langendorff-heart) were followed by in vivo experiments (rat) investigating toxicity and pharmacokinetic. Most interestingly, relevant changes in systemic parameters during and after i.v. infusion of nanocapsules were not detected. Microvascular perfusion and oxygen supply by erythrocytes remained unaffected. Parameters indicating tissue impairment did not show any life-threatening deviation. Intravascular half-life of nanocapsules was satisfactory. The subsequent “proof-of-concept” study (rat) to demonstrate the functionality in the complete animal was successful. All animals treated with nanocapsules survived the gradual exchange of about 95% of blood much better than control animals.

Barbara Palazzo

Ghimas S.p.A. c/o Dhitech Scarl, Campus Ecotekne, Italy

Title: Nanostructured ceramics for bone cancer therapy

Time : 12:25:12:50

Speaker
Biography:

Barbara Palazzo has completed her PhD in Chemistry in 2006 from Bologna University and Postdoctoral Studies from Oriental Piedmont University, Medical Science Department. She is responsible for the local research unit of Ghimas S.p.A in the High Tech District of Lecce. She is author of more than 35 papers in peer review journals. Her research is focused on biomimetic inorganic and polymeric materials intended for the repair of defects in the maxilla-facial site or in the osteochondral unit. She investigates multifunctional nanomaterials for the controlled delivery of chemotherapeutic agents, above all for the treatment of bone tumors and metastasis.

Abstract:

Bone cancer, is among the most invasive tumors with lowest survival probability. In this case, following cancerous bone excision, concealing the bone tissue loss is necessary and to this aim materials designed for bone replacement are requested. Moreover, a subsequent antitumor treatment needs to be carried out to avoid recurrence. This review talk will focus, three particular strategies, all of them aimed to address the therapeutic treatment to the tumour site: 1. The employment of ceramic nanoparticles as targeted anticancer drug carriers to be exploited as injectable devices. Particularly the speech will include calcium phosphate and silica-based materials intended for hosting and carrying anticancer molecules, due to their particular surface nanostructure. 2. the use of those nanomaterials that we can define as “intrinsically anticancer” because they possess some properties that can activate specific cellular mechanism, and specifically, they can act as nano-thermoactuators for hyperthermia or as small sources of radiation. 3. the use of nanobioceramics as bone fillers with anticancer function to be implanted into the affected piece of bone. This talk section will illustrate the combination of both the above described approaches: magnetic phases are included into implantable bioceramics in order to obtain composites that can be designed for skeletal reinforce and contemporarily act in order to prevent metastases after tumour resection. Starting from nanostructured bioceramics composition and functional properties, the results presented in this talk will describe the mechanism through which they may be adjuvant in the multifaceted curative techniques that must be adopted against bone tumours. 

Break: Lunch Break 12:50-13:20 @ Hotel Restaurants
  • Young Reasearch Forum
Location: OLIMPICA 4

Session Introduction

Ruba Ismail

University of Szeged, Hungary

Title: Up to date advances in nano-carrier systems for oral delivery of antidiabetic peptides

Time : 14:10-14:25

Speaker
Biography:

Ruba Ismail has completed her Master’s study in Pharmaceutical Sciences in 2015 from Tishreen University, Latakia, Syria. Presently, she is a 1st year PhD student at Szeged University, Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, Szeged, Hungary.

Abstract:

Current progresses in pharmaceutical biotechnology have led to the discovery of numerous antidiabetic peptides. Nevertheless, these drugs like insulin, GLP-1 and its analogs are currently administrated parenterally, a route which is not well accepted by patients, and also does not mimic the endogenous pathway of insulin or GLP-1 secretion. Aiming to overcome the various disadvantages of this delivery route, tremendous efforts have been recently devoted for oral antidiabetic peptides administration. Based on the evaluation of recently published papers, it can be concluded that among numerous approaches to enhance the antidiabetic peptide oral bioavailability, much of the success was recorded using different nanocarrier systems including solid lipid nanoparticles, micelles, polymeric nanoparticles, liposomes and nanoemulsions. A successful nanocarrier should protect the peptide from the harsh environment within the GIT, and facilitate both mucus permeation and epithelial absorption. Besides, there is an integral need to prove that the benefits of these nanosystems overweight their risks, further in vivo and human studies must be conducted to know more about the effect of these carriers on the pharmacokinetics and efficacy of antidiabetic drugs. Despite these significant research efforts, there is still no FDA approved oral insulin or GLP-1 analog on the market. Thus, research in this area should be continued at even a higher pace to access a safe and effective nanosystem that could be completely accepted for chronic treatment of diabetes. This review emphasizes the challenges, advantages and limitations of different possibilities with a critical thinking and aiming to select the proper way for further steps in the field.

Speaker
Biography:

Annalisa Dalmoro carries out her research work in TPP group at the University of Salerno on novel processes for the production of dosage forms and on the development of materials for biomedical applications. In particular, she focused her work on the design and building of a semi-continuous bench-scale apparatus for the production of shell-core microparticles combining two non-conventional technologies, such as ultrasonic atomization and microwave drying; on the production of micro and nano systems by exploiting ultrasonic energy; on the synthesis of enteric polymers for pharmaceutical applications; on the study about the crosslinking phenomena of biopolymers, thus about their applicability for in situ coating of coronary stents. Moreover, she was also involved in studies on granulation processes, stabilization of food by spray drying, and on fruits, grains and legumes processing by microwaves, through collaborative projects with companies.

Abstract:

Statement of the Problem: The large interest in the development of lipid and polymeric micro- and nano- drug delivery vectors lies in their properties of minimizing drug loss or degradation, reducing side effects, improving drug biodistribution and penetration in cellular compartment. Different advanced preparation techniques are currently used, however as all modern manufacturing processes also pharmaceutical industry must respond to the mandatory rules of sustainable productions. Therefore it is moving to the intensification of production processes, included those based on nanotechnologies, i.e. to process miniaturization, capital cost reduction, and improvement of energy use and final product quality. Among the tools to achieve this objective, ultrasonic energy has the potential for the improvement of production techniques of lipid and polymeric carriers on micro and nano scale.

Methodology & Theoretical Orientation: Ultrasonic atomization and sonication were the method used for the “intensified” production of drug delivery vectors, respectively. The fundamentals of both were analyzed in order to understand the mechanisms at the basis of micro- and nano- vectors formation and sizing.

Findings: The ultrasonic energy was a potent tool able to produce vectors encapsulating different active molecules, in particular to: 1) produce enteric shell-core microparticles by energy-saving ultrasonic atomization, 2) make stable double emulsions for the production of polymeric micro- and nanoparticles, 3) size the final dimension of liposomes, according to the application requirements.

Conclusion & Significance: Advantages and novelties introduced by the use of ultrasonic energy in preparative methods of lipid and polymeric vectors were put in evidence by proving that the ultrasonic-based techniques are versatile and promising for the successful preparation of stable, highly loaded formulations, avoiding any harsh preparative conditions or large amount of solvents.

Speaker
Biography:

Abdulrahman M Elbagory holds a MSc in Organic Chemistry from the University of the Western Cape (UWC) in 2015 in which he was awarded the National Research Foundation (NRF) fellowship. His Master’s study was about the chemical isolation and characterization of natural products from marine animals. His research included in vitro antiproliferation activity of the isolated secondary metabolites against cancerous cell lines and investigating their apoptosis properties. Currently, he is in third year of his PhD in the Department of Biotechnology (UWC), which is funded by the NRF and DST/Mintek Nanotechnology Innovation Centre. His PhD study is about the green synthesis of metallic nanoparticles from plants and their anticancer and antibacterial evaluations. He has two publications as first author and one review as a co-author.

Abstract:

Statement of the Problem: The preparation of gold nanoparticles (AuNPs) involves a variety of chemical and physical methods. These methods use toxic and environmentally harmful chemicals and procedures. Consequently, the synthesis of AuNPs using green chemistry has been under investigation to develop eco-friendly and biocompatible nanoparticles using plant-derived phytochemicals. Several green synthesized AuNPs have been shown to have antibacterial effect. There is growing need for effective and safe antimicrobial agents to treat infected deep wounds. The aim of this study was to green synthesize AuNPs from plants, evaluate their antibacterial activity against skin wound infection bacteria including methicillin-resistant Staphylococcus aureus and also measure their toxicity on human normal fibroblast cell line (KMST-6).

Methodology: The AuNPs were biosynthesized according to Elbagory et al. (2016) from aqueous extracts of the South African Galenia africana and Hypoxis hemerocallidea plants. The AuNPs were characterized using Ultra Violet-Visible Spectroscopy, Dynamic Light Scattering and High Resolution Transmission Electron Microscopy. The antibacterial activity of the biosynthesized AuNPs were tested using Alamar blue assay. The toxicity of the biosynthesized AuNPs was evaluated in vitro using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay.

Findings: Spherical AuNPs were formulated ranging in size from 15 to 25 nm in diameter (Figure 1). The AuNPs from H. hemerocallidea were shown to have antibacterial activity against the tested bacteria strains except Salmonella sp., whereas Galenia-AuNPs only exhibited antibacterial activity against Pseudomonas aeruginosa (Table 1). Both AuNPs showed no toxicity on KMST-6 cells at the highest tested concentration (32 nM) after 24 hrs treatment.

Conclusion & Significance: Different AuNPs were successfully synthesized from plants using green nanotechnology. The results reveal that these AuNPs have antibacterial effects that can be safely employed in wound infections.

Speaker
Biography:

Nicole R S Sibuyi obtained her PhD degree in Biotechnology from University of the Western Cape (South Africa) where she is currently enrolled as a Postdoctoral Research Fellow under DST/Mintek Nanotechnology Innovation Centre (Biolabels Unit). Her research interests range from biomarker discovery, proteomics, targeted nano-based therapy and drug delivery. Her research is mainly focused in identifying biomarkers for chronic diseases such as cancer, diabetes and obesity. These disease-associated biomarkers will be used for the development of diagnostics as well as personalized therapy using Nanotechnology. Her research interests had advanced into Green Nanotechnology after she had received 3 months training in the application of green nanotechnology in cancer therapy at the Institute of Green Nanotechnology, Missouri University (Columbia, USA). They (Biolabels Unit) are currently using Green Nanotechnology for synthesis of biocompatible metallic nanoparticles using indigenous medicinal plants.

Abstract:

Development and progression of chronic diseases such as obesity and cancer, is dependent on angiogenesis for nutrients and oxygen supply to diseased cells. As such, pharmacological inhibition of angiogenesis is therefore a sensible strategy for treatment of these diseases. The aim of this study was to develop targeted anti-angiogenic gold nanoparticles (AuNPs) that can be delivered selectively to the target cells and trigger the apoptotic cell death. The AuNPs were bi-functionalized with a targeting peptide and a pro-apoptotic peptide. The targeting peptide (adipose homing peptide, AHP) used in the study binds to a protein that is overexpressed by endothelial cells in the white adipose tissue (WAT) vasculature of obese subjects. We previously evaluated the bio-distribution of nanomaterials functionalised with the AHP and demonstrated that these nanoparticles accumulated in the WAT of animal models of obesity. In the current study, the bi-functionalized AuNPs were synthesized then characterised by UV-Vis, Zeta potential and TEM. The selective targeting and toxicity of the targeted-AuNPs was investigated on three human cancer cell lines (Caco-2, MCF7 and HT29), of which Caco-2 cells express the cell surface receptor for AHP. The AuNP toxicity on cells was evaluated using the WST-1 and the APO Percentage assays, while the AuNP uptake was confirmed by ICP-OES analysis. The AuNP cytotoxicity was more pronounced in the cells expressing the receptor for AHP, the Caco-2 cells. The uptake of the bi-functionalized AuNPs was higher on target cells, the bifunctionalized AuNPs showed receptor mediated targeting and targeted destruction of Caco-2 cells following apoptosis pathway. The bi-functionalized AuNPs demonstrates potential for the development of targeted anti-angiogenic strategy for the treatment of obesity and possibly also colon cancer. The therapeutic efficacy and specificity of bi-functionalized AuNPs in animal models of obesity and cancer is underway.

Speaker
Biography:

Congcong Lin has her expertise in development of novel drug delivery system and passion in improving the health and wellbeing. Her main research direction is design and evaluation of the new drug delivery system based on the special microenvironment of tumor sites to achieve targeted drug delivery and precision therapy. She has developed triptolide-loaded liposomes decorated with anti-carbonic anhydrase IX (CA IX) antibody targeting CA IX confined to cancerous cells to increase the accumulation of the drug loaded liposomes at tumor sites and combining the advantage of pulmonary delivery for better retention of active ingredients in lung. This study provides insight into targeted and sustained delivery of a toxic drug through CA IX-decorated liposomes via the pulmonary route for lung cancer therapy.

Abstract:

Statement of the Problem: Lung cancer is one of the most common lethal malignancies worldwide with 1.59 million deaths each year. Low accumulation of therapeutic agents in the tumor site and lack of penetration ability of a drug delivery system into tumor masses are the main obstacles in efficient lung cancer therapy.

Aim: The purpose of this study is to enhance the efficacy of anti-cancer drug against lung cancer by targeting carbonic anhydrase IX (CA IX) confined to cancerous cells to increase the accumulation at tumor sites and combining the advantage of tumor homing cell penetrating peptide (CPP33) to promote the penetration of the drug loaded liposomes into lung cancer cells.

Methodology & Theoretical Orientation: Anti-CA IX antibody and CPP33 dual-ligand triptolide-loaded liposomes (dl-TPL-lip) were developed using the post-insertion technique. The characteristics of dl-TPL-lip including particle size, entrapment efficiency and drug release property were carried out. The effects of dl-TPL-lip on NSCLC cells were evaluated by wound healing and apoptosis assay. Moreover, the penetrating ability and inhibition efficacy of dl-TPL-lip were further investigated using 3D tumor spheroids.

Findings: The dl-TPL-lip displayed the optimal efficacy in inducing apoptotic feature of NSCLC cells, which showed tunable size (137.6±0.8 nm), high encapsulation efficiency (86.3±2.6) and sustained release. The superior penetrating ability and inhibitor effect on 3D tumor spheroids were also observed for dl-TPL-lip.

Conclusion & Significance: The data suggest that dual-ligand modification with anti-CA IX antibody and CPP33 on the surface of liposomes endow great potential for lung cancer therapy.

Speaker
Biography:

Xue Zhang has her expertise in liposomal drug delivery systems in improving chemotherapeutic drug properties and for targeted cancer treatment. She has developed a cancer cell-specific liposomal carrier by modifying liposomal surface with a cancer cell-specific penetrating peptide. And also she evaluated the therapeutic efficacy and effectiveness of this carrier in vitro (2D and 3D cells) and in vivo hepatocellular carcinoma model.

Abstract:

Statement of the Problem: Nowadays liver cancer has become the second leading cause of cancer related death globally. Systemic therapy with chemotherapeutic agents has severe toxicity to normal cells and the application is limited in pre-clinical study. Researchers have reported that liposomal drug delivery system working as a carrier by encapsulating chemotherapeutic agents into its hydrophobic or hydrophilic parts can enhance the bioavailability and solubility of drugs, facilitate the tumor-specific targeting treatment purpose with surface modification, and further reduce the drug toxicity to normal tissues. However, these delivery systems have not been adopted in clinics. The purpose of this study is to develop cancer-cell specific penetrating peptide modified liposomal delivery system with CTD encapsulated for targeted hepatocellular carcinoma treatment.

Methodology & Results: The cancer cell-specific penetrating peptide (CCP) modified-liposome prepared in the present study had a particle size around 120 nm and a narrow polydispersity index. It had an enhanced cytotoxicity on HepG2 cells compared to the control, free drug and unmodified liposome by MTT assay. In addition, a provoked apoptosis was induced by this liposome as well. The cellular uptake results of HepG2 and normal Miha cells further confirmed the higher ability of the CCP-modified liposomes to penetrate cancer cells. A higher efficiency of delivery by CCP-modified liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor 3D spheroids penetration and inhibition experiments as well as the in vivo study. In conclusion, our CCP-modified liposomes improve the anticancer potency of drugs for hepatocellular carcinoma.

 

Speaker
Biography:

Julia Ernst is a Pharmacist by training and graduated at the Friedrich Schiller University Jena in 2012. After gaining practical experience in pharmaceutical industry, hospital and public pharmacy in Switzerland and Germany, she started her PhD studies in 2014 at the Department of Pharmaceutical Technology, FSU Jena. Her research is focused on formulations for nanoparticular drug delivery systems to the lungs.

 

Abstract:

Antimicrobial treatment is a cornerstone of cystic fibrosis (CF) therapy, as approximately 90% of CF patients die from lung destruction promoted by pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia. However, the efficacy of the inhaled antibiotics is limited due to a hindered penetration of drugs through mucus and bacterial biofilms which is difficult to imitate in vitro. In our experiments we developed a way to overcome these barriers, by loading tobramycin (Tb) into biodegradable poly(lactic-co glycolic acid) based nano- (NP) and microparticles (MP) modified with PEG and a blue fluorescent dye (AMCA) to investigate the penetration in mucus and the antibiotic efficacy in bacterial biofilms. Tb-loaded particles of 830 nm (MP) or 230 nm (NP) and zeta potentials of ca. -10 mV were prepared by a double-emulsion evaporation method and characterized by SEM and HPLC. For biofilm experiments, bacteria were cultivated in artificial mucus (AM)-containing chamber slides to allow the formation of a biofilm close to those of CF patients or in a microfluidic device to imitate the physiological shear flow in the body. The excellent penetration abilities of Tb-loaded particles through AM and biofilms and the remarkable antimicrobial efficacy in comparison to the free drug was confirmed by confocal laser scanning microscopy of LIVE/DEAD® stained biofilms. In conclusion, we demonstrated that the NP and MP displayed excellent properties as biocompatible, mucus-penetrating delivery systems for antibiotics with improved deposition and bacterial killing of biofilm-embedded pathogens even under more physiological conditions compared to conventional in vitro models.

Break: Networking and Refreshments Break: 15:55-16:10 @Foyer

Pegah Esmaeilzadeh

Martin Luther University of Halle-Wittenberg, Germany

Title: A responsive thiolated polysaccharide multilayer nanocoating for tuning cell adhesion and cell detatchment

Time : 16:10-16:25

Speaker
Biography:

Pegah Esmaeilzadeh researches in the field of synthesis and characterization of single-walled natural protein nanotubes, and their byproduct architectures such as protein nanofibers, nanospheres, and nanoparticles have been successfully developed in nanotechnology section of RIPI of Tehran (Research Institute of Petroleum Industry). She was also active in different research projects on ZnO quantum dots as novel antibacterial, antifungal, or anticancer drugs. She is currently PhD student in Institute of Pharmacy in Martin Luther University Halle Wittenberg in Germany, and receiving new experiences in medical nanocoatings/interfaces/thin films and particularly cell studies.

Abstract:

Advanced efforts in the design of responsive biomedical coatings are focused on the decoration of surfaces with functionalities that promote a predetermined biological response such as modulating cell adhesion and proliferation as well as cell detachment. Following this aim, we synthesized a stimuli-responsible cell carrier nano-coating system with multilayers made of thiolated chitosan (t-Chi) and thiolated chondroitin sulfate (t-CS) units. This redox-responsive multilayer system was realized by intrinsic cross-linking triggered by oxidative stimuli, while these bridges were prone to dissociation under reductive conditions. It is remarkable that this chemical changes were fully reversible as demonstrated by repeated oxidation and reduction (Oxi-to-Re) or in opposite from reduction to oxidation (Re-to-Oxi) cycles. The physical properties of multilayers during these treatments were studied by in situ spectroscopic ellipsometry and liquid-based atomic force microscopy and surface plasmon resonance showing changes of layer thickness and elastic modulus. Since protein adsorption is a prerequisite of cell adhesion, binding of fibronectin was studied with a fluorescent labeling technique. Correspondingly, the novel multilayer nano-coating was used to define the human dermal fibroblast cell microenvironment and the impact of switching cycles on cell adhesion and detachment events was verified. The latter is presented briefly in figure 1. As this thiolated polymeric system is responsive to the body’s internal stimuli like pH and redox, it holds great promise for medical applications and stimuli-sensitive drug delivery systems.

Sophie Franceschi

Université Paul Sabatier, France

Title: Evaluation of organogel nanoparticles as new vehicle for lipophilic compounds

Time : 16:25-16:40

Speaker
Biography:

Sophie Franceschi has her expertise in chemical and physicochemical studies of organized molecular systems for drug delivery and material applications. She has 20 years of experience in research and teaching. She graduated with a PhD from the Paul Sabatier University of Toulouse (France) in 1997 and has a Master’s degree in Molecular and Supramolecular Chemistry. Currently, she is Researcher in SMODD group in the IMRCP Laboratory at the University Paul Sabatier of Toulouse and also Teacher at Paul Sabatier University.

Abstract:

In recent years, a growing interest has emerged in the development of semi-solid colloidal careers for the delivery of water-insoluble drugs. Solid lipid Nanoparticles (SLN) and Nanostructured Lipid Careers (NLC) are example of such systems. As an alternative to SLN, we propose the use of an original family of organogel nanoparticles. Organogels are semi-solid materials in which an organic solvent (e.g., vegetable oil) is entrapped in the three-dimensional fibrous network formed by self-aggregation of a low molecular mass organic gelator (12-Hydroxystearic acid). The preparation process of the gelled oil nanoparticles is based on the sol-gel phase transition of the organogel obtained by hot emulsification (T°>T°gel) in presence of an aqueous solution of stabilizing agent (Polyvinylalcohol 80), leading to a stable semi-solid dispersion after cooling (T°In vitro dialysis release experiments showed different kinetic profiles in comparison with control buffer solutions, underlying the importance of the drug solubility in the gelled oil and its possible ionization in water. The results obtained have enabled us to evaluate the drug delivery capabilities of these gelled particles and their possible use in different pharmaceutical pathways (oral or skin).