Biomedical 2017 October 16-17, 2017 Osaka, Japan

Biography:

Mr. Dan Liu has completed his Masters degree in Chemical Engineering at the age of 25 from Temple University in Philadelphia, USA and he obtained his MBA degree at the age of 30 from University of Iowa. He is currently the process engineer at Patheon Inc., a leading contract manufacturing organization (CMO) in the USA specializing in Active Pharmaceutical Ingredient manufacturing. He has held several patents and been invited to numerous research focused symposium worldwide. He has significant knowledge in API manufacturing in a controlled cGMP environment.

Abstract:

Novel statistical tools have been applied to the manufacturing industry, process design/engineering and other industries for more than two decades. These tools are frequently used in process optimizations as well as the diagnosis of various process failures. The goal of using statistical techniques in a manufacturing environment is to improve the process efficiency and ultimately increase the batch consistency and/or reduce the overall project cost. This paper is to use a case study in a cGMP (curernt Good Manufacture Practice) pharmaceutical manufacturing environment to demonstrate how statistic techniques could be deployed to diagnose the bottleneck of a continuous manufacturing process. Multivariate analysis was used as a novel statistical tool to illustrate how variables to a process could affect the yield of an Active Pharmaceutical Ingredient (API) manufacturing process. Our results suggested that human factor (HF) variable such as lead operator involvement, positive-emotion operator participation will have a positive influence on the final API yield, while operator mentality variable such as knowing holiday approaching and numbers of operators in a production shift will have a negative impact on the API yield (AY). We also examined technical factor (TF) variables specifically related to the chemical process in this case such as temperature, holding time, pH, etc., we discovered that only certain yield critical variables will have the influence on the final API yield where explanations were given using reaction mechanism. Finally, we investigated cGMP factors (GF) variables such as the number of deviations issued, the number of supplements issued, the number of corrective actions and preventative actions (CAPA) issued, and the number of cGMP documentation corrections, the results suggested only certain GF variable will bear statistical significance against the API yield. We also documented the various level of statistical influence on independent variable such machine time (MT) using the same HF, TF and GF factors variables and we also proposed statistical relationship of those dependent variables against MT. We then proposed my recommendations as to how to increase the process yield and reduce the machine time strategically.

Biography:

Prof. Yongxiang Zhao is the innovative leading talent of National "Ten Thousand Talent Programme", the director of the National Center for International Research of Biological Targeting Diagnosis and Therapy, the moderator of the BIT’s 5th World Gene Convention Keynote Forum---Nobel Laureate Forum. He has taken charge of 14 national science and technology major projects and 16 provincial and ministerial projects.

Focus on biological targeting diagnosis and therapy for tumor, including: 1. The  key targets and mechanism of malignant tumor’s occurrence and progress. 2. Homologous antitumor vaccines. 3. Research and development of heterologous oncolytic biological drugs. 4. Research and development of tumor biotargeted diagnostic reagents.

Based on these research results, 79 SCI papers have been published in international journals, such as Nature Biotechnology (IF=41.67), and so on. One International Academic Award, one ministerial and provincial first prize, thirty national patents and two authorized international PCT patents.

Abstract:

Background: Tumor vessels can potentially serve as diagnostic, prognostic and therapeutic targets for solid tumors. Fluorescent dyes are commonly used as biological indicators, while photobleaching seriously hinders their application. In this study, we aim to generate a fluorescent silica nanoparticles (FSiNPs) theranostic system marked by the mouse endgolin (mEND) aptamer, YQ26. Methods: A highly specific YQ26 was selected by using gene-modified cell line-based SELEX technique. FSiNPs were prepared via the reverse microemulsion method. The YQ26-FSiNPs theranostic system was developed by combining YQ26 with the FSiNPs for in vivo tumor imaging, treatment and monitoring. Results: Both in vitro experiments (i.e. cellular and tumor tissue targeting assays) and in vivo animal studies (i.e. in vivo imaging and antitumor efficacy of YQ26-FSiNPs) clearly demonstrated that YQ26-FSiNPs could achieve prominently high targeting efficiency and therapeutic effects via aptamer YQ26-mediated binding to endoglin (END) molecule. Conclusion: This simple, sensitive, and specific YQ26-FSiNPs theranostic system has a great potential for clinical tumor targeting imaging and treatment.

Biography:

Dr. Eunjoo Kim (Ph.D.- Environmental Toxicology), now is an Principal Research Scientist of Companion Diagnostics and Medical Technology Research Group, DGIST. She got her BS and MS in biochemistry at Yonsei University, and Ph.D. in Environmental Toxicology at Seoul National University, Korea. Currently Dr. Kim’s researches focus on the circulating biomarkers and nanomedicine, especially for the development of diagnostic and therapeutic tools based on non-invasive biomarkers and nano-bio materials. She also concentrates in developing new types of biomarkers and their detection system for liquid biopsy, such as exomes and circulating tumor cells based on nano-bio technologies. 

Abstract:

Molecular changes during aging have been studied to understand the mechanism of aging progress. Herein, changes in miRNA expression in the whole blood and exosomes of mice were studied to systemically reverse aging and propose as non-invasive biomarkers. Through next generation sequencing analysis, we selected 27 differentially expressed miRNAs in whole blood of mice during aging. The most recognized function involved was liver steatosis, a type of non-alcoholic fatty liver disease (NAFLD). Among 27 miRNAs, six were predicted to be involved in NAFLD, miR-16-5p, miR-17-5p, miR-21a-5p, miR-30c-5p, miR-103-3p, and miR-130a-3p. The expression of the genes associated in the network of these miRNAs, Bcl2, Ppara, E2f1, E2f2, Akt, Ccnd1, and Smad2/3, was also altered in the liver of aged mice. Following transfection of these miRNAs into old mice, levels of transfected miRNAs in liver increased, and expression of Mre11a, p16INK4a, and Mtor, reported to be aging-associated molecules, was also reversed in the livers. In case of exosomal transfection from young to old mice, similar results were obtained. The identified molecules in whole blood and exosome might induce a reverse-regulation of aging-associated pathways. This study provides preliminary data on reverse-aging, which could be applied further for treatments of adult diseases.

Biography:

Claudia Moraes de Rezende is a professor/ researcher at the Chemistry Institute of UFRJ, dealing with natural products chemistry and spectroscopy, and she is also the vice-president in the Brazilian Society of Mass Spectrometry (BrMass).

Abstract:

Leishmaniasis is a public health problem in 98 countries and its therapy is based on pentavalent antimonials, pentamidine, amphotericin B and miltefosine. For all of them high toxicity, elevated cost and parasite resistance have been reported. Natural products are potential sources of novel active molecules that may provide structural template for drug discovery. Studies showed that coffee intake may be effective against heart and coronary disease, Parkinson's and Alzheimer's. Cafestol and kahweol (C&K) are two natural coffee diterpenes with antitumoral, antiinflammatory and antioxidant activities. The aim of this study was to evaluate the effect of C&K together and separately against Leishmania amazonensis. Cytotoxicity of C&K (1:1) for host cells was investigated by the XTT method. Our results demonstrated a CC50 of 26.9µg/mL. Besides, C&K presented an anti-L. amazonensis activity with an IC50 of 4.7µg/mL for promastigote forms, while for intracellular amastigotes the IC50 was 12.3µg/mL. The C&K selectivity index was 2.19. Our results showed that C&K does not induce nitric oxide (NO) production on macrophages infected with L. amazonensis, moreover, reduced 2.1-fold the NO production on IFN-γ and LPS-activated macrophages. To rule out a possible NO scavenger effect of C&K, a cell-free system was used with SNAP as a NO donor in the presence or not of C&K, and these drugs were not able to reduce NO levels. However, they increase 2.1-fold the production of reactive oxygen species in infected macrophages. Our data point C&K as promising substances for the development of a drug with leishmanicidal activity.

Biography:

angmun Shin has his expertise in quality by design and its associated statistical analyses in pharmaceutical science. He has also developed a number of robust design estimation and optimization methods in order to find the robust factor settings for various manufacturing and pharmaceutical processes. Improvement of pharmacokinetics and pharmacodynamics evaluation precision is his new research direction.

Abstract:

In order to improve the quality of a drug product, International Conference on Harmonization (ICH), United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) have suggested a various guidelines and Quality by Design (QbD) platforms. To this end, the main objective of this research is to conduct comparative analyses among those platforms. In addition, this research proposes a new QbD platform and its associated guideline. This proposed QbD platform includes six steps: Quality target product profile (QTPP), critical quality attribute (CQA), risk assessment (RA), design space (DS), control strategy (CS), and life cycle management (LM). In addition, this research also provides a number of statistical design and analysis methods, such as quality function deployment (QFD) for CQA procedure, failure mode and effect analysis (FMEA) for the RA procedure, design of experiment (DoE) and response surface methodology (RSM) for design and operating spaces generation in the DS procedure and robust design optimization methods to reduce process variability. Finally, this research demonstrates possible solutions for existing scale-up problems for commercial pharmaceutical manufacturing processes.

Biography:

Andre van Zyl has obtained his Postgraduate studies as a Specialist in Oral Medicine and Periodontics from the University of Stellenbosch, Cape Town, South Africa. He is currently the Head of Department of Periodontics and Oral Medicine at the University of Pretoria, South Africa. He is also the Chair of the International Team for Implantology Center of Excellence at Pretoria and also Chair of the ITI Scholarship Center.

Abstract:

Introduction & Aim: The engineering of dental implant surfaces has shown tremendous development over the past decade. Bone-to-implant interface is influenced mainly by implant surface topography. The objective was to analyse the exact surface area of different implant diamters of 5 systems using micro-focus cone beam tomography.

Methods: 100 implants were scanned at Necsa (South African Nuclear Energy Corporation) which houses the Nikon XTH 225 ST micro-focus CT scanner. The spatial resolution obtained is 1-3 μm instead of 300 μm for CBCT. To obtain a high quality 3D-virtual image at this high spatial resolution, the number of 2D projections increases from 375 to 8000. Analysis was done using VGStudioMAX-3.0 visualization software (Volume Graphics GmbH, Heidelberg, Germany).

Results: Statistical analysis showed Ankylos had the largest mean implant surface area (151.90 mm2) in the narrow platform (NP) group and Neodent the smallest (125.95 mm2). Megagen implants had the largest surface area (227.39 mm2) in the regular platform (RP) group and Neodent the smallest (164.25 mm2). Statistically significant differences (P<0.001) were found between systems.

Conclusion: NP implants have become important in order to avoid complex bone augmentation procedures. It is therefore important for surgeons to know the exact surface area of NP versus RP implants. The greater the surface area of implants, the less pressure on the surrounding bone, which is of importance from a biomechanical point of view. This is the largest study of its kind using micro-focus CT technology and can be used as a reference for future studies. There is currently no reliable data on total implant surface area.

Biography:

Yaw Opoku-Damoah is a PhD Researcher at the Chinese Academy Sciences, Shanghai Institute of Materia Medica. He has received his Masters in Pharmaceutics from the China Pharmaceutical University, Nanjing, China. As part of his National Service, he has worked with the Import and Export Control Department of the Food and Drugs Authority, Ghana, West Africa before being awarded a Joint Chinese Government Scholarship/Ghana Government Scholarship to pursue Postgraduate studies in Pharmaceutics. His research is focused on biopharmaceutics, nanotechnology, drug delivery and theranostics. He is specifically interested in the use of nanotheranostics for site-specific delivery and diagnosis of tumors. He has publications in high impact factor journals such as Biomaterials and Theranostics.

Abstract:

The emergence of nanotechnology comes with a grave concern about efficacy, toxicity and side effects. Even though chemotherapy, surgery and radiation therapy have been able to provide valuable assistance in clinical treatment, there is a pressing need for novel bio-friendly drug delivery systems which can eliminate all the constraints related to the traditional treatment regimen. This present work encompasses drug targeting via reconstituted high-density lipoproteins, combined chemotherapy and photodynamic therapy as well as in vitro nano inspired theranostics. We successfully synthesized zinc oxide-bound paclitaxel (ZnO/PTX) and packaged the photochemotherapeutic formulation into high-density lipoproteins via one-pot synthesis. The final rHDL/ZnO/PTX nanomedicine had a characteristic near-spherical shape and a particle size of 164.9±2.8. A zeta potential of-19.94±1.73 as well as percent drug loading of 12.75% demonstrated that the nanoformulation could be an efficient in cancer drug delivery system. FTIR analysis proved that ZnO was successfully bound to PTX via hydrogen bonding before subsequent co-encapsulation in the lipid core. We further determined the UV absorbance and fluorescence spectra of our formulation. The PTX and ZnO drug release pattern was assessed by two methods and analyzed by HPLC and ICP-OES analysis, respectively. The results suggested that ZnO could remain intact in neutral solutions but could slightly dissolve in acidic and harsh dissolution media to trigger the collapse of the nanoparticle. The in vitro antitumor efficacy on adenocarcinomic human alveolar basal epithelial cells (A549 cells) was evaluated by MTT assay and flow cytometry. The results suggested that the terminal nanoparticle could control the release of drugs and maximize the cancer cell toxicity. The final nanoparticles irradiated with UV light proved to be the most efficient treatment relative to the other groups. It was also deduced that UV light may be used for photodynamic therapy as an improvement for the antitumor efficacy of rHDL/ZnO/PTX. This was further confirmed by the quantitative and qualitative detection of ROS which serves as an apoptotic tool. Confocal laser scanning microscopy was used to detect the presence of ROS with the help of DCFH-DA ROS detection kit, and the resulting images suggested that rHDL/ZnO/PTX could produce significant quantities of reactive oxygen species. Flow cytometry analysis confirmed that the fluorescence was more conspicuous in cells that were irradiated with UV light as compared to cells incubated with rHDL/ZnO/PTX and rHDL/PTX. We further employed Annexin V FITC Apoptosis kit and flow cytometry to evaluate the existence of apoptotic and necrotic cells after incubating drugs with various drug formulations. We also utilized the ZnO fluorescence to track intracellular trafficking with both active and passive targeting. This study further confirmed that rHDL/ZnO/PTX could be harnessed for UV light-mediated photochemotherapy while ApoA-I could help facilitate the shuttling of drugs into cancer cells via SR-BI receptors. In addition, we demonstrated that ZnO could be used as a potential in vitro theranostic moiety while mediating photodynamic therapy and pH-responsive drug delivery. Herein, we were able to establish that our nano-based in vitro theranostic platform could be a robust, safe, stable and efficient nanodelivery system which could be developed for future cancer therapy and diagnosis.

Biography:

Abdul Hafeez has completed his MPharm in Pharmaceutics from Teerthankar Mahaveer University, Moradabad, India and pursuing his Doctoral studies from Glocal University, India in Pharmaceutics Department. He has published more than 10 papers in reputed journals and has been serving as an Editorial Board Member of repute. He is a Member of reputed pharmaceutical societies like Association of Pharmaceutical Teachers of India (APTI) and Indian Pharmacy Graduate Association (IPGA).

Abstract:

Melanoma is one of the types of cancer of skin which generates from the pigment cells known as melanocytes of skin and covers global economic burden for the treatment. Regular exposure of skin of genetically susceptible person to ultra-violet radiation range is the main cause of induction of melanoma in skin. Dacarbazine which is chemically imidazolecarboxamide is utilized as a drug of choice for the treatment of melanoma as well as Hodgkin's lymphoma cancer. Dacarbazine induces programmed cell death (apoptosis) in the cancerous cells of melanoma by inhibition of synthesis of DNA. Major drawback with this drug is its poor solubility in water, short shelf-life in systemic circulation, low rate of response and severe adverse effect which limits its utility. In this study, Dacarbazine in the form of nanoformuation (size >100 nm) was utilized for augmenting the anticancer effect of chemotherapeutic drug. In current study Dacarbazine nanostructured lipid particles (DTIC-NLPs) were prepared by solvent diffusion method. In drug release study, the drug shows depressed release in free form in comparison to DTIC-NLPs after 48 hours in PBS (pH 7.4). MTT assay shows its strong cytotoxic potential as compare to simple Dacarbazine suspension.

Biography:

Vipan Kakkar received the bachelors degree in electronics engineering from Nagpur University, India; masters degree from Bradford University, UK, in 1997, and doctorate from Delft University of Technology, the Netherlands. He worked at Phillips, the Netherlands, as R&D engineer and system architect in various System‐on‐Chip projects for 8 years. Since 2009, he has been faculty with the Department of Electronics Engineering, Shri Mata Vaishno Devi University, Katra, India. His research interests include nanotechnology, ultra low‐power analog and mixed signal design, microelectromechanical (MEMS) systems design, synthesis and optimization of digital circuits, biomedical system and implants design, and audio and video processing. He is a Senior Member of the IEEE and Life Member of the ISTE and has served as an Executive Council Member of IEEE, Delhi, India, and has developed IPs, and published many research papers in peer‐reviewed journals and international conferences.

Abstract:

Implantable Medical Devices (IMDs), especially biosensors research is still in its early stages, and thus represents an enormous opportunity for which Ultra Low Power System on Chip (SoC) and VLSI/MEMS technologies can enable the development of novel devices and therapies. Broadly, biomedical implants encompass a range of medical solutions for various bodily disorders and include Cardiovascular implantable devices such as defibrillators, pacemakers; Neural devices like deep brain stimulation (DBS) and prostheses for central nervous system (CNS), peripheral nervous system (PNS), cochlear and retinal applications; Biosensors include miniaturized glucose sensor, cholesterol sensors, saliva sensors etc. are picking up in the research arena. Unlike other commercial devices however, developing microsystems for these applications requires critical analysis in terms of specifications, technologies and design techniques because of the devices’ safety and efficacy. The trade-off between performance and power consumption is a challenging act in the design of these devices. This presentation aims to evaluate possible applications, to derive the requirements that future circuits integrating bio-sensors, ultra low power processors, must meet and to recognize, as far as possible, the challenges which have to be faced.