25^th Nano Congress for Future Advancements August 16-18, 2018 Dublin, Ireland

Biography:

Joong Tark Han has completed his PhD from Pohang University of Science and Technology. He is the Center Director of Nano Hybrid Technology Research Center at KERI in Korea, and a Professor of Department of Electro-Functionality Materials Engineering at UST. He has published more than 90 papers in reputed journals.

Abstract:

Flexible electrodes fabricated with conducting soft electromaterials such as carbon nanotubes (CNTs), graphene and metal nanowires are of great interest for various applications, ranging from alternative electrodes for flexible electronics. However, the difficulty in processing these soft electro materials represents one of the key challenges to researchers working in this area. In this talk, author will present his recent progress in synthesis of nanocarbon hybrid materials and their processing technologies for applications in flexible electrode technology towards soft electronics. The judicious use of supramolecular chemistry and interfacial engineering technology allows fabrication of printable, spinnable, and chemically compatible conducting pastes with high-quality nanocarbon (NC) materials, useful in flexible electronics and textile electronics.

Biography:

Silvia Panseri is a Biologist and has completed her PhD in 2009 at the University of Milan, Italy. Her research activity is mainly focus on nano and regenerative medicine. She has great expertise in cell-biomaterial interactions at the nanoscale, in magnetic cell guiding and 3D cell culture in bioreactor with several scaffolds. She is an author of more than 50 papers published in international peer-reviewed journals, 12 book chapters, co-inventor of two patents and H-index=19. She has been serving as a Guest Editor in International Journal of Molecular Sciences and Frontiers in Bioengineering and Biotechnology.

Abstract:

Cell therapy is one of the most exciting and promising areas for disease treatment and regenerative medicine. However the success rate of cell-based therapies, despite their great potential, is limited mainly due the ineffective delivery and retention of therapeutic cells in the specific organ. Magnetic targeting has emerged as a method to overcome these limitations. So far these attempts have used superparamagnetic iron oxide nanoparticles (SPIONs), only clinically approved metal oxide nanoparticles. Nevertheless the exposure to SPIONs has always been associated with significant toxic effects such as inflammation, apoptosis and generation of ROS. Our group, by doping hydroxyapatite (HA), the mineral component of bone, with Fe²⁺/Fe³⁺ ions, had obtained novel biocompatible and fully bioresorbable superparamagnetic nanoparticles (FeHA). This work demonstrates the opportunity of FeHA in mesenchymal stem cells (MSCs) labeling. MSCs easily internalized the FeHA, and they became magnetic enough to be guided and retained to specific site by a magnet. Magnetic MSCs maintained their morphology and cell viability was not negatively affected. Due the well-known osteoinductive feature of HA, magnetic MSCs overexpress osteogenic genes. We are also investigating the possibility to combine these above-mentioned results with the contrast ability of FeHA for a real time imaging of the magnetic MSCs in vivo by magnetic resonance imaging. In conclusion, due to the intrinsic magnetic properties of FeHA, its fast degradation and very low iron content compared to SPIONs, this approach could be simply transferred to different cell types obtaining an attractive advanced approach for several regenerative medicine applications.

Biography:

Ying Wan received her Ph.D. degree in Industrial Catalysis from the East China University of Science and Technology in 2002. Then, she joined Shanghai Normal University where she was promoted to a full professor in 2006. In 2005-2007, she carried out her postdoctoral research at Fudan University working with Professor Dongyuan Zhao. Currently, Professor Ying Wan is the leader of the Program for Innovative Research Team in University, China. Her research focuses on sintering-, and poisoning-resistance metal nanocatalysts supported on mesoporous carbons, and their applications in green organic synthesis and energy chemistry. She has contributed to about 70 peer-reviewed scientific publications with more than 7000-times citations and 3 books. She has been an associate editor of Journal of Porous Materials since 2013.

Abstract:

Gold nanocatalysts represent a new generation of catalysts for the selective oxidation and reduction using molecular O₂ and H₂, showing great potentials for green chemistry. Activated carbons are one of the most frequently used supports in industry. However, activated carbon has been seldom used for gold deposition. Here a coordination-assisted self-assembly approach is adopted for the intercalation of thermally reduced gold nanoparticles inside ordered mesoporous carbon frameworks. An almost complete conversion of benzyl alcohol to benzoic acid is achieved within 60 min over the Au/C catalyst with gold nanoparticles approximately 9.0 nm under 90 ºC and 1 MPa, using potassium hydroxide as a base. A reduction of gold particle size from 9.0 to 3.4 nm in the catalyst leads to a high activity toward the selective oxidation of benzyl alcohol to benzyl acid and toward the reduction of p-nitrophenol to p-aminophenol at low temperatures such as 0 °C. The electronic modification of the d-orbitals of small particles is extremely important for chemisorption of O₂ at atmosphere pressure and low temperatures. Interstingly, thermally reduced Au/C nanocatalyst with gold nanoparticles approximately 2.8 nm is highly active and selective to convert p-chloronitrobenzene and 4-nitrophenol to corresponding amines using H₂ as a reducing agent, reaching an initial reaction rate of 12.7 and 6.5 min^-1, respectively. By comparison, the commercial Au/C catalyst is inert under the same reaction conditions. Trapping by the SH-functionalized SBA-15 solids confirms the negligible gold leaching and the heterogeneous active centers for thermally reduced Au/C. Obvious changes are undetected for catalytic performance after five runs. These results indicate that the gold-containing mesoporous carbon catalyst is stable and can be reused. The simultaneous thermal reduction of gold nanoparticles and pyrolysis of the matrix may facilitate the involvement of gold inside the carbon matrix, the modification of carbon atoms on the gold surface, and the reconstruction of the surface induced by CO adsorption. The generation of low-coordinated gold atoms possibly reduces the H₂ dissociation barrier, and can therefore significantly improve the hydrogenation activity.

Biography:

Monica Montesi has obtained her PhD in Cellular and Molecular Biology at the University of Bologna and she has 12 years of expertise in cellular and molecular biology associated to material science for nanotechnology, tissue engineering research and regenerative medicine. She is a scientific coordinator of NanoBioMagnetism Laboratory. She is an author of 40 papers published in international journals, several book chapters and more than 30 congress communications. She has been serving as an Editorial Board Member of international Journal of Bone and Mineral Metabolism and Guest Editor of International Journal of Molecular Sciences.

Abstract:

The ever increasing need of more effective and targeted therapies for the treatment of cancer and various degenerative pathologies is pushing material scientists to develop new solutions associating enhanced safety with smart functionality, also permitting the establishment of personalized therapeutic approaches. In this respect, the development and use of nanoparticles is today limited by several factors among which: i) low biodegradability and biocompatibility; ii) toxic by-products; iii) uncontrolled drug release into the bloodstream; iv) limited cell-target specificity and v) low efficiency in crossing biological barriers. In this respect a novel apatite based nanoparticle (NPs) have attracted the attention of scientific community for biological and medical purposes as promising materials in drug or gene delivery, DNA/biomolecules separation, hypothermal treatment of tumours, contrast agents for imaging, and recently in tissue engineering and theranostic applications. Recently, novel biomimetic, fully biodegradable and cytocompatible NPs fabricated by doping hydroxyapatite (HA) with Fe ions (FeHA), avoiding the presence of magnetic secondary phases and coating, were developed and biologically tested as new drug delivery systems. The wide possibility of surface functionalization of apatitic nanoparticles significantly extends the potential to develop smart drug carriers with active or passive ability to cross physiological barriers and to reach relevant organs such as the brain, the lung or the heart.

Biography:

Madaswamy S Muthu earned his Bachelor’s Degree in Pharmacy in 2002; Master’s Degree in Pharmaceutical Technology from India in 2004 and PhD Degree in Pharmaceutics from IIT, Varanasi, India in 2009. He did his Postdoctoral trainings in the Department of Chemical Engineering at National University of Singapore as a Recipient of Boyscast Fellowship and CREST Award from India. He is also an Awardee of DST Young Scientist in 2012. His research interest is to develop advanced nanomedicine as novel platform for diagnosis and therapy. He has authored over 64 peer-reviewed publications with a cumulative impact factor of >240, citation of 2100 and h-index of 24.

Abstract:

Nanotheranostics have shown the development of advanced platforms that can diagnose cancer at early stages, initiate first-line therapy, monitor it, and if needed, rapidly start subsequent treatments. In nanotheranostics, therapeutic and diagnostic agents are loaded with nanomedicine in a single theranostic platform, which can be further developed as clinical formulations for targeting different types of cancer. This speech is concerned about theranostic micelles developed using TPGS (tocopheryl polyethylene glycol succinate), docetaxel and gold nanoclusters for the early diagnosis and therapy of cancer with advanced features. Micelles are amphiphilic spherical nanostructures consisting of hydrophilic shell and hydrophobic core. Micelles have advantages such as thermodynamic stability, kinetic stability, higher payload and smaller dimension (less than 50 nm). In our group, various research studies were done on targeted micelles for cancer diagnosis and therapy. In future, nanotheranostics will be able to provide personalized treatment which can make cancer even curable or at least treatable at the earliest stage.

Biography:

Lorenz De Neve started his carrier as a Researcher with his master thesis on the sorption behavior of cationic surfactants. During this period he obtained experience concerning the preparation and characterization of liposomal dispersions, including viscometry using rotational viscometers, submicron particle sizing by dynamic light scattering and adsorption analysis by both QCM-D and by the traditional depletion technique. Currently he is conducting research on pharmaceutical nanosuspension formulations. More specifically the purpose of his research is to enlarge the fundamental knowledge of the link between the formulation parameters and the macroscopic properties of nanosuspensions and to understand the interactions between the different formulation parameters.

Abstract:

Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer surfactants (poloxamers or pluronics) are used as stabilizer in various nanosuspensions, e.g. of rilpivirine, danazol, diclofenac, asulacrine and itraconazole. In order to have a stabilizing effect on hydrophobic particles, these PEO-PPO-PEO surfactants should adsorb to the particle surface. In this research, the adsorption behavior of pluronics with two different ethylene oxide contents (50% and 80%) and three different molecular weights of the propylene oxide part (i.e. 950, 1750 and 3250 g/mol) was studied at 20°C and 37°C onto gold sensors coated with 1-undecanethiol using a quartz crystal microbalance with dissipation (QCM-D). Pluronic solutions with 5 different concentrations were used, ranging from 0.02 mg/ml to 50 mg/ml. Our results indicate a significant (linear) effect of the pluronic concentration on the average adsorption during the adsorption steps. No clear effect could, however, be detected after rinsing of the sensors with ultrapure water. The molecular weight of the PPO part seemed to have a proportional effect on the adsorbed amounts after rinsing, but no clear effect during the adsorption steps. The ethylene oxide content seemed to have an effect during both the adsorption and rinsing steps. Also, our results indicated no significant difference in the average adsorbed amount during both the adsorption and rinsing steps at 20°C and 37°C. The obtained results were useful to gain more insight in the stability differences between nanosuspensions with different pluronic concentrations (and molecular structure).

Biography:

Robert Prudhomme is a Professor in the Department of Chemical and Biological Engineering at Princeton University, USA. He is the Founding Director of the Program in Engineering Biology. His research program focusses on polymer self-assembly applied to drug delivery. The development of Flash Nanoprecipitation (FNP) in his laboratory enabled the encapsulation of poorly soluble drug compounds and oligonucleotides for therapy directed towards cancer, TB, and injections. FNP is a scalable and continuous process that is enables integrated processing and spray drying for low cost oral and aerosol formulations. Under sponsorship by the Bill and Melinda Gates Foundation, the process is being adopted to formulate new compounds coming from TBA, MMV, and DNDi.

Abstract:

There is an increased demand for fast and inexpensive methods to determine cancer phenotypes and morphologies. Current in vivo diagnostic imaging modalities utilizing X-ray CT, MRI, and PET scans are limited to black-white images that cannot be used to differentiate multiple disease marker contrast agents at a time. In addition, targeting studies in which each nanoparticle (NP) type must be individually administered to an animal result in large numbers of animals that must be used in a study to obtain reliable statistics. This requires both significant time and expense. Photoacoustic (PA) imaging, a hybrid light and sounds imaging technique, has shown to be a safe and inexpensive diagnostic technique with high spatial resolution in 3D. Traditional PA contrast agents, however, tend to have broad absorption peaks in the NIR range which renders it difficult to simultaneously image more than one signal at a time in deep tissue. Here we present the formulation of a series of PA active NPs with sharp and separable absorbance profiles in the NIR range for simultaneous multiplexed imaging. PA dyes are encapsulated inside NPs using the controlled self-assembly mechanism, Flash nanoprecipitation (FNP). Four new contrast agents, with sharp absorbance maxima between 600-900 nm, were created by encapsulating a variety of phthalocyanine derivatives. We were able to simultaneously detect the concentrations of contrast agents mixed together with >95% deconvolution efficacy. As a proof of concept, we co-injected RGD modified NPs and non-modified NPs with different labeling agents and tracked NP biodistributions for both particles simultaneously. Using this technology, we accessed the effect of NP ligand modification on both targeting efficacy onto the tumors and off targeting accumulation in the liver using a single animal model. Over modification of the NPs resulted in rapid liver clearance and poor accumulation in the tumor; at low modifications, the tumor to liver accumulation ratio is 9.9±4.2, while at high RGD modifications the tumor to liver accumulation ratio is 52±22. The ability to simultaneously inject control particles and targeted particles, and to follow their fate greatly enhances the ability to design targeted nanoparticles. The same phthalocyanine dyes effectively chelate PET active cations to enable whole animal PET imaging. The FNP technology enables the production of both NPs that enable PAI and PET imaging. 

Biography:

Tamás Solymosi holds an MSc Degree in Chemical Engineering and currently working on his PhD thesis about the formulation of abiraterone acetate. He has been working at NanGenex, Budapest, Hungary for the past 9 years, gaining experience in the formulation of poorly water soluble active ingredients. He is interested in the physicochemical background of nanoformulation and bioavailability increasing technologies.

Abstract:

Abiraterone acetate (AA) is a poorly water soluble drug molecule indicated for metastatic castration resistant prostate cancer. The drug product Zytiga possesses the highest food effect of all marketed drugs. Despite of the extremely poor absorption of AA in fasted conditions, Zytiga is to be taken strictly without food. We have developed a nano-amorphous abiraterone acetate formulation prepared by controlled precipitation followed by lyophilization. The formulation exhibited higher apparent solubility and passive permeability when compared to either the crystalline AA or Zytiga. DLS (Dynamic Light Scattering) measurements and filtration experiments yielded particle size in the 100-200 nanometer range when the solid formula was reconstituted in water. The active ingredient in the formulation was amorphous by XRD (X-ray Powder Diffraction). Beagle dog studies showed 10-fold increase in exposure from the novel formulation when compared to the marketed drug. Also, the marked food effect seen with Zytiga was not observed for the nano-amorphous AA. A first-in-human clinical trial was conducted with a lyophilized powder-in bottle formulation in healthy male volunteers. The active ingredient was rapidly absorbed in both the fasted and the fed states. Based on the PK (Pharmacokinetics) analysis a 250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. As in preclinical studies, the significant positive food effect was eliminated. Moreover, variability of exposure was reduced when compared to Zytiga. In conclusion we have developed a novel nano-amorphous AA formulation that significantly outperformed the marketed product in in vitro and in vivo tests. Ultimately, the formulation might allow a 75% dose reduction and negate the restriction of a food label.

Biography:

Nilay Kahya completed her MSc Degree in Chemistry at ITU Graduate School of Science Engineering and Technology in 2016. She is currently a PhD candidate working under the guidance of Professor F Bedia Erim Berker. Her research field of interest are mainly related to the applications of biopolymers in drug delivery systems and adsorption fields. She has four publications in Science Citation Index Expanded journals by March 2018.

Abstract:

Alginate is a biopolymer which is used in several biomedical applications by means of its favorable properties, such as biodegradability, biocompatibility and non-toxicity. In the present study, the availability of alginate gel to encapsulate and release a protein type drug was investigated. The use of alginate has been reported before for the controlled release of bovine serum albumin (BSA), however favorable controlled release behavior was only achieved by the help of clay incorporation to alginate beads. Recently, it was reported that incorporation of anionic surfactant, sodium dodecyl sulfate (SDS) into alginate increases the Young’s modulus of the alginate beads. Moreover, SDS and bovine serum albumin interaction via complexation mechanism was reported. In the light of the last two works, SDS was incorporated into alginate beads to enhance protein-loading efficiency of hydrogel and to prevent the burst release of protein drug. Bovine serum albumin (BSA) was used as model protein drug. It was found that SDS modified calcium alginate beads encapsulated almost the initial amount of loaded drug. The protein release experiments were done in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Results of release experiments showed that SDS modified alginate beads showed controlled and time efficient drug release. Characterization of the beads was performed by Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), and swelling experiments, respectively.

Biography:

Lucyna Matusewicz graduated with MSc in Biotechnology in 2012. She is currently a PhD student at the University of Wroclaw, Poland. She started her PhD project and for almost 6 years has been focusing mainly on drug delivery systems in anticancer therapy.

Abstract:

Introduction: Epidermal growth factor receptor (EGFR) was shown to be highly expressed in many types of human cancer, among others, in breast cancers. EGFR overexpression correlates with advanced stage of the disease and with poor response to chemotherapy. One of the promising strategy for the treatment of EGFR-dependent tumors is to inhibit signal transduction from EGFR via disruption of cholesterol rich membrane rafts. We assume that targeted delivery of simvastatin, a popular cholesterol-depleting drug widely prescribed in the treatment of cardiovascular diseases, will specifically disorganize membrane rafts and therefore disturb the EGFR dependent signalling pathways that usually promote cell proliferation and metastases. Statins were shown to exert antitumor effects in high doses, but those may lead to serious side effects. Therefore, the main purpose of this work is to obtain targeted, long circulating liposomes with simvastatin and to test their anticancer activity both in vitro and in vivo.

Methodology: Liposomes were prepared via lipid film hydration method and modified by attachment of antibodies specific to EGFR. Stability, selectivity and toxicity of targeted liposomes were analyzed both in vitro and in vivo. The level of activation of selected kinases involved in transduction of signals stimulated via EGF in cells treated by immunoliposomal statin was examined. Moreover, changes in plasma membrane order of cells exposed to liposomal simvastatin were examined using FLIM (Fluorescence-lifetime imaging) method.

Findings: Designed immunoliposomes were stable over 6 months, selective towards EGFR overexpressing cells and showed antitumor efficacy both in vitro and in vivo. Inhibition of signaling pathway involving Akt in cells treated with immunoliposomal simvastatin and disruption in plasma membrane order were observed.

Conclusions: Presented immunoliposomal formulation of simvastatin seems reasonable solution of a specific delivery of high doses of this drug into tumor cells and a candidate of further evaluation for efficacy either in monotherapy or in combination in anticancer therapies in the future.

Biography:

Jong Seok Woo has completed his PhD from Kyungpook University. He is the Manager of Morgan Advanced Materials in Korea. He has published more than 20 papers in reputed journals.

Abstract:

A smart multifunctional surface of conductive plastics with a superhydrphobic surface having porous micro- and nano-structures can potentially be very useful in many applicatioins of electrostatic dissipation (ESD), electromagnetic interference (EMI) shielding, and in transparent film heaters with self-cleaning properties. Here, we demonstrate a facile and rapid method for fabricating superhydrophobic conductive films from transparent conductive films with silver nanowires (AgNWs) and single-walled carbon nanotubes (SWCNTs) on polycarbonate (PC). This process involves the swelling of the PC surface in a dispersion of multi-walled CNTs (MWCNTs) in methly ethyl ketone (MEK), followed by coaqulation in isopropy alcohol (IPA, nonsolvent for PC). During swelling, the AgNWs and SWCNTs migrated into the plastic, and after that, the swollen PC chains were crystallized in IPA. Notably, by adding MWCNTs in MEK, the crystallization of PC chains was accelerated, and the rapid increase in the eletrical resistivity of the films was minized by reducing the formation of microstructures. Crystallization of the AgNW/SWCNT electrode onto PC and the incorporation of MWCNTs during crystallization provided a flexible superhydrophobic heater for use as a self-cleaning surface. Our results provide a very easy way to fabricate a conductive and superhydrophobic polymer surfaces with lotus-like bionic nanostuctures.

Biography:

Keith H Moss holds a BSc Degree in Biochemistry and Genetics from the University of Cape Town, RSA and an MSc in Engineering (Biotechnology) from the Technical University of Denmark (DTU). Currently, as a first year PhD student at DTU, he is engaged in the development of a novel technology platform for the identification of optimal nanoparticles for therapeutic applications. This project encompasses multiple disciplines and incorporates his interest in human disease and molecular therapeutics as well as nanotechnology and pharmaceutical drug development.

Abstract:

Conventional, untargeted and nonspecific therapies, especially regarding cancer, are commonly associated with a low therapeutic index due to poor drug efficacy and significant adverse effects. Nanoparticles (NPs) as drug delivery vehicles represent a promising strategy to overcome such shortfalls. Development in the field of NPs and clinical translation for therapeutic applications has been limited by technical and regulatory factors. Currently, there are unmet needs in the design, generation and screening of therapeutic NPs such as a consistent and reproducible synthetic technique capable of up-scaling. This is, in part, due to the vast array of parameters that each requires optimization. As a result, current strategies to optimize NPs for therapeutic applications are low-throughput and experimentally time consuming. Nucleic acids and other “hard to drugify” therapeutic macromolecules have been restricted to highly personalized therapeutic strategies such as chimeric antigen receptor (CAR) therapy and other adoptive cell therapy (ACT) applications. A breakthrough regarding the field of CAR T cell therapy would be an in vivo administration approach, which could potentially transform an expensive, patient specific therapy to a generic and widely-available treatment strategy, without the need for patient T-cell gene modification and expansion ex vivo. Such an innovative approach would utilize NPs to systemically deliver messenger RNA (mRNA), encoding for CARs targeting surface antigens expressed on cancer cells to T cells. The CodeSphere platform technology represents a unique strategy to generate and screen for optimized NP/liposome formulations in a high-throughput manner. The novelty in this proposed technology is the use of a DNA barcode as a unique liposome identifier. This DNA-barcode molecular-encoding system was previously developed by Bentzen et al., for the large-scale detection of antigen specific T cells and is now being applied in this new platform. In essence, liposomes will be tagged with a unique DNA barcode encoding for and identifying the composition. The CodeSphere strategy involves the generation of large, diverse DNA-encoded NP libraries which can then be screened in a single-tube assay, allowing the simultaneous assessment of thousands of different NP formulations for the most effective delivery of therapeutic cargo.

Biography:

Robert Prudhomme is a Professor in the Department of Chemical and Biological Engineering at Princeton University, USA. He is the Founding Director of the Program in Engineering Biology. His research program focusses on polymer self-assembly applied to drug delivery. The development of Flash Nanoprecipitation (FNP) in his laboratory enabled the encapsulation of poorly soluble drug compounds and oligonucleotides for therapy directed towards cancer, TB, and injections. FNP is a scalable and continuous process that is enables integrated processing and spray drying for low cost oral and aerosol formulations. Under sponsorship by the Bill and Melinda Gates Foundation, the process is being adopted to formulate new compounds coming from TBA, MMV, and DNDi.

Abstract:

Biologics, the fastest-growing sector of the pharmaceutical marketplace, are an attractive class of therapeutics because of their impressive potency, high selectivity, and reduced off-target effects. But while the effectiveness of these drugs outclasses many of their small-molecule predecessors, administering biologics remains a challenge. Physiological barriers such as chemical digestion (when taken orally), rapid blood clearance (when injected), or thick pulmonary mucus (when inhaled) chemically or physically prevent biologics from reaching their targets and working as designed. To reduce the frequency of dosing, strategies of protecting these proteins and peptides within delivery vehicles have arisen, but the majority of these processes suffer from high losses and poor scalability. We here present a scalable and continuous method of encapsulating water-soluble charged biologics into polymeric nanoparticles. This is done by simultaneously reversibly ionically modifying the biologics of interest with hydrophobic counterions and controllably precipitating the newly-formed hydrophobic complex into nanoparticles via the polymer-directed Flash NanoPrecipitation technique. This combined technique, termed hydrophobic ion pairing Flash NanoPrecipitation (HIP-FNP), is applicable to a wide variety of peptides and proteins, both anionic and cationic. Importantly, the process is continuous, scalable, and achieves encapsulation efficiencies greater than 95%. We herein demonstrate encapsulation of two model proteins: the cationic enzyme lysozyme (MW 14,300 D) and the anionic protein ovalbumin (MW 42,700 D). By altering the identity or amount of hydrophobic counterion used, we can tune protein release rates, an important consideration for prolonged delivery. Importantly, we also show that the proteins’ activity has been retained throughout the processing steps. We believe this technique offers a route forward for improving the delivery of many biologic therapeutics and may improve patient comfort and compliance by simplifying dosing regimens.

Biography:

Juliana Damasceno Oliveira completed her Bachelor’s Degree in Pharmacy. She is currently a PhD student in the Department of Biochemistry and Tissue Biology at the Institute of Biology of University of Campinas (UNICAMP), Brazil. She has experience in the areas of pharmacology, biochemistry and pharmaceutical technology - working in the development of drug-delivery systems, DDS, mainly ionic gradient liposomes – and biophysical methods applied to the study of the structural, physicochemical, mechanical and biological properties of DDS.

Abstract:

Statement of the Problem: Liposomes are lipid carriers widely used in drug-delivery, and a number of liposome-based products have been approved for clinical application, so far. Local anesthetics interact with liposomes, distributing themselves in the lipid bilayer and in the inner aqueous core, prolonging the anesthesia time. In ionic gradient liposomes (IGL) the ionizable drug is loaded in preformed vesicles that exhibit a trans-membrane ionic gradient leading to high drug upload and, subsequently, prolonged drug release.

Objectives: The objective of this work is to develop IGL for the sustained release of etidocaine (EDC).

Methodology: Large unilamellar vesicles (LUV, 20 mM) composed of soy phosphatidylcholine:cholesterol (6:4 mol%) plus 250 mM sulfate gradient, were prepared for the upload of 0.5% EDC. Dynamic light scattering (DLS), nanotracking analysis (NTA) and transmission electron microscopy (TEM) were used to characterize the liposomes’ size, polydispersity (PDI), zeta potential (PZ) and number of particles. The in vitro release of EDC was measured in Franz diffusion cells, at 37°C. Cell-viability assays were done in primary cell cultures (Schwann or sciatic nerve cells from Wistar rats).

Results: IGL were successfully prepared with size, PDI, PZ and concentration in the range 500 nm, 0.2 and -20 mV, and 4-5.10¹², respectively, and they kept stable over 60 days at 37±37°C. TEM data revealed the spherical morphology of the liposomes that was able to encapsulate 41% of EDC. At 37°C, the time for 100% release of the anesthetic increased from 3 h (EDC in solution) to 24h in IGL_EDC. Cytotoxicity tests revealed that encapsulation into liposomes decreased the intrinsic toxicity of the anaesthetic.

Conclusions: IGL are very interesting carriers for the delivery of local anesthetics. In this study sulphate-gradient LUV (large unilamellar vesicles) were found promising increase the upload, and release of etidocaine. In vivo tests are under course to evaluate the antinociceptive effects of the formulation.

Biography:

Samaneh Kabirian, a Chemist completed her Bachelor’s Degree in Pure Chemistry; Master’s Degree in Analytical Chemistry (detection of biomolecule in blood). She has her expertise in synthesis, characterization of nanoparticles conjugated to aptamers and passion in improving its application in biology of cancer. She is always curious and enthusiastic to work on multidisciplinary project and bridging gap between different domains of science. She is currently pursuing a double degree PhD in Molecular and Cellular Biology at the University of Lyon (France) and in Analytical Chemistry at Isfahan University (Iran). She has been studying and working in biochemistry and biology laboratory of cancer research center of Lyon (France) for the past 3 years. She gave her a good point of view to biological aspects of applications of nanoparticles in biology of cancer. With strong background in chemistry and specially analytical chemistry, she is also trained in all common molecular and cellular biology manipulations like cell culture, protein and DNA analysis and so on. Her double skilled ability helps build a good connection in multidisciplinary project especially cancer biology and pharmaceutical chemistry.

Abstract:

AS1411 is a G-rich oligodeoxynucleotide aptamer that has been used in phase II clinical trials for the potential treatment of cancers. Forming a G-quartet structure, AS1411 binds to cell surface nucleolin specifically, and is subsequently internalized into the tumor cell. It remains unclear how AS1411 binding to nucleolin leads to cell proliferation inhibition and cell death. Despite remarkable AS1411 results in a few patients, the overall rate of response has been low, possibly because it has less than optimal pharmacology and relatively low potency. Attaching AS1411 to gold nanospheres (AS1411-GNSs) increases its accumulation in cancer cells and enhances its antitumor efficacy by binding to cellular nucleolin. Nucleolin is associated with ribosomal DNA (rDNA) and is absolutely required for rRNA synthesis. It binds with nanomolar affinities the G-quadruplex rDNA sequences to increase the rate of RNA polymerase I (POL1) transcription. We developed a new complex of AS1411 conjugated to Gold nanospheres (GACGs). This complex was more stable and effective than AS1411 in treated tumor cell lines. GACGs decrease nucleolin expression affecting tumor cell proliferation and POLI targeting genes transcription such as 5’ETS and 18s. Thus, GACGs targeting Nucleolin/rDNA complexes inhibit POLI and represents a novel, nucleolar targeting approach to selectively disrupt proliferation in cancer cells and induce cell death.

Biography:

Robert Prudhomme is a Professor in the Department of Chemical and Biological Engineering at Princeton University, USA. He is the Founding Director of the Program in Engineering Biology. His research program focusses on polymer self-assembly applied to drug delivery. The development of Flash Nanoprecipitation (FNP) in his laboratory enabled the encapsulation of poorly soluble drug compounds and oligonucleotides for therapy directed towards cancer, TB, and injections. FNP is a scalable and continuous process that is enables integrated processing and spray drying for low cost oral and aerosol formulations. Under sponsorship by the Bill and Melinda Gates Foundation, the process is being adopted to formulate new compounds coming from TBA, MMV, and DNDi.

Abstract:

Nanotechnology in drug delivery has a schizophrenic dichotomy of goals. One goal is to make drugs more bioavailable, which is normally associated with oral drug delivery. This bioavailability is associated with rapidly releasing drugs. The goal is achieved by making nanocarriers (NCs) with high surface-to-volume ratios, and with the drug in an amorphous state. The other goal is to encapsulate and deliver drugs to specific disease sites. This requires retaining the drug in the NC until targeted delivery is achieved. We will discuss examples of nanoparticle formulations based on our rapid micromixing platform – Flash Nanoprecipitation  (FNP)– that address both of these goals. Targeted, sustained-release NCs require degradable block copolymers that enable targeting, but also clearance. Sustained release is achieved either by making insoluble ion pairs or through pro-drug synthesis. Enhanced dissolution, for oral delivery of poorly bioavailable therapeutics, requires the development of low-cost NC stabilizers. We demonstrate NC formation using lecithin, HPMC, and the corn protein, zein. The coupling of FNP to a spray drier enables a continuous, integrated, one step and scalable process for the production of powders for oral administration. The unexpected stability of these NC powders to high temperature and humidity, and the scalability of the platform were major reasons that the Gates Foundation has funded our group to prepare NC formulations of several drugs coming through their pipeline. While FNP was initially developed for encapsulation of hydrophobic actives, soluble peptides and proteins are now the fastest growing segment of the pharmaceutical market. We will present a new inverse Flash Nanoprecipitation process (iFNP) which enables encapsulation of peptides and biologics at 90% loading with 95% loading efficiency. The encapsulation at these loadings has not been achieved by other technologies.

Biography:

Regina Herma is PhD candidate at Jan Evangelista Purkyne University(UJEP),Czech Republic. Her work is mainly focused on the effect of type, generation and surface modification of carbosilane dendrimers on the interaction with selected nucleic acids for applications in biomedicine (transport molecules for drug targeting, vectors for gene therapy, potential treatment of lung cancer). She is part of a research team for a number of projects.

Abstract:

Gene therapy is a rapidly growing field of biomedical research which has sparked great interest because it offers the possibility of a permanent cure a variety of genetic-based diseases. The success of gene therapy depends on the development of suitable vectors for the delivery nucleic acids into cells. Our work is focused on the comparative study of the two types of cationic carbosilane dendrimers terminated with the ammonium and phosphonium groups for their use as non-viral vectors for siRNA transfection. We present a part of work devoted to characterization of dendriplexes formed from generation 1-3 (G1-3) of carbosilane dendrimers and model siRNA. We used a number of biophysical methods (e.g. Gel retardation electrophoresis, DLS, ξ (zeta)-potential, AFM) for characterization of dendriplexes. Transfection efficiency was evaluated by Fluorescence Microscopy and Flow Cytometry. Both types of dendrimers G2-G3 form stable complexes with siRNA due to positive charge of surface groups of dendrimers and negative charge of siRNA backbone. Formation of dendriplexes was investigated at different charge ratio (1/5 – 10/1 (+/-)) to find the optimal properties of complexes (e.g. stability, surface charge, dimensions) for transfection of cells. In vitro transfection experiments proved the ability of both G3 dendriplex structures to enter the cells, with maximal achieved transfection efficiency at 7/1 (+/-) charge ratio. Ammonium dendrimers achieved max. 30% of transfected cells. More than 70% of cells were transfected under the same conditions with phosphonium terminated dendrimers. With the aim to optimize the properties of phosphonium dendriplexes we incorporated new periphery substituents (P(Et₂)₂(CH₂)₃OH, P(Ph)_3, P(C₆H₄-OMe)₃, PBu₃) into dendrimer structure. Similar cytotoxicity (except PBu₃₎ and transfection efficiencies were obtained with the exception of P(Ph)₃ peripheral substituent. This type of dendrimer exhibits more than 80% transfection efficiency and seems to be the “hot” candidate for further improvements of gene delivery by phosphonium carbosilane dendrimer vectors.