Day 1 :
Keynote Forum
Abraham Atta Ogwu
University of the West of Scotland, UK
Keynote: Visible light activated silver oxide antimicrobial coatings with potential orthopedic and medical implant applications
Time : 10:00-10:40
Biography:
Abraham Atta Ogwu is the Chair of Biomaterials, Thin Film Devices and Nanotechnology at the University of the West of Scotland (Former Paisley University). He leads the Engineering and Biomedical Coatings Research Group in the Institute of Thin Films, Sensors and Imaging (former Thin film Centre), School of Engineering and Computing. He is a Fellow of the UK Institute of Physics and the UK Institute of Materials, Minerals and Mining. He has previously worked at the School of Materials, Manchester University, England, UK; in the School of Engineering and the former Nanotechnology Institute of the University of Ulster and the Engineering Research Institute, Northern Ireland, UK.
Abstract:
One of the best and most utilized semiconductor photo-catalyst reported currently in literature is titanium dioxide. Titanium dioxide has many advantages as a photo-catalyst such as low cost, availability, chemical and photochemical stability. It is however having a band gap of about 3.1 ev and is activated using ultraviolet radiation which is costly to generate. Several attempts have been made to develop photo-catalysts activated using visible light, but the development of a photo-catalyst that is cheap enough and activated using visible light, has remained a major challenge to date. We have prepared optically transparent and visible wavelength photo-catalytically activated antimicrobial silver oxide thin films using reactive magnetron sputtering. Our X-ray diffraction analysis of the films confirmed the presence of two phases Ag2O and Ag4O4 reported in literature to have antimicrobial properties. The chemical composition and stoichiometry of the films was monitored with Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) using the peak shape of the Ag3d5/2 and Ag3d3/2 binding energy peaks. Spectrophotometry was used to determine the optical band gap in the visible wavelength range and confirm up to 80% optical transmission in the visible in the films. The release of silver ions in water and saline solution by the films was confirmed with atomic absorption spectroscopy measurements. Microbial cell adhesion and growth on the films was imaged with the scanning electron microscope (SEM). We also confirmed complete microbial cell deaths of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus aureus within 20 minutes on exposure to the silver oxide films using killing curve measurements. The mechanism of bacterial attack by the films can be associated with silver ion release, the ease of ligand replacement in the silver oxide stoichiometry and their exchange and interference with biological ligands in the microbes. Silver ion replacement of metals in the biochemical complexes in bacteria can alter their structure, function and dynamics leading to bacteria death. Our current finding opens the door to furthering the development of non-ultraviolet (UV), but visible light activated antimicrobial surfaces. The silver oxide films also have the potential to be incorporated as an antimicrobial layer with controlled ion release on orthopedic and medical implant coatings
Keynote Forum
Bryan J McEntire
University of Utah, USA
Keynote: Bacteriostatic behavior of silicon nitride, polyether ether ketone and titanium biomaterials
Time : 10:40-11:20
Biography:
Bryan J McEntire is a Chief Technology Officer for Amedica Corporation. He has previously served as the Vice President of Manufacturing and Vice President of Research. He has received his BS and MBA degrees in Materials Science and Engineering and Operations Management, respectively from the University of Utah and his PhD from the Kyoto Institute of Technology. He has more than 35 years of industrial experience in research, development and production of advanced ceramics, including positions at Ceramatec, Salt Lake City, USA, Saint-Gobain Industrial Ceramics Corporation, Northboro, MA and E Granby, USA, Applied Materials Corporation, Santa Clara, USA and at Amedica Corporation, USA. He is the author and co-author of over 65 peer reviewed publications and holds 8 patents. He is an Emeritus Member and Fellow of the American Ceramic Society.
Abstract:
Statement of the Problem: Perioperative and latent infections (PJI) are leading causes of revision surgery for orthopedic devices. They are a growing problem due to the rising antibiotic resistance of bacteria to germicidal therapies. An in vitro test was developed to compare biofilm formation on three biomaterials, polyether ether ketone (PEEK), a titanium alloy (Ti6Al4V-ELI) and a series of surface-modulated silicon nitride (Si3N4) bioceramics using Gram-positive Staphylococcus epidermidis (S. epidermidis) and Gram-negative Escherichia coli (E. coli).
Methods: Several variants of Si3N4 (Amedica Corp., Salt Lake City, UT, USA), PEEK (ASTM D6262) and Ti-alloy (ASTM F136) discs (Ø12.7 mm × 1 mm) were characterized, cleaned, UV sterilized and exposed to 105 bacteria cultures of either S. epidermidis (ATCC 14990) or E. coli (ATCC 25922) for 24 and 48 hours. They were then vortexed, plated and incubated at 37 oC for 24-48 hours, followed by comparative bacterial colony counting.
Results: The two bacterial biofilm tests are presented in Figure 1 and 2 for S. epidermidis and E. coli, respectively. A two-tailed, heteroscedastic student’s t-test (95% confidence) was used to determine statistical significance. The highest density of CFUs was always found on the PEEK biomaterial, followed by the Ti-alloy and then the various Si3N4substrates. Biofilm growth on PEEK was between 2-3 orders of magnitude greater than on the Ti-alloy or any of the Si3N4 materials (all p<0.005). Ti6Al4V also had more bacteria than the Si3N4 samples, but it was not significant in all cases.
Conclusion: Development of bacteriostatic biomaterials is one of many important prosthetic device strategies to combat PJI. Si3N4 shows considerable promise in its inherent ability to inhibit bacterial attachment and biofilm formation and as a result, it represents a significant advancement over traditional biomaterials.
Discussion: Attachment of bacteria to biomaterial surfaces is complex and correlations to single parameters are often difficult to assess. A multivariate approach is necessary because microbial adhesion is not only related to the bacterial strain itself, but also affected by the biomaterial’s surface topography, charging, wetting behavior, chemistry and the in vivo environment (e.g., serum proteins, nutrients and fluid-flow conditions). In each of these categories, the various Si3N4 materials examined within this study appear to have appropriate surface and chemical characteristics to inhibit biofilm establishment, including sub-micron and nanoscale topography, improved wetting, large negative surface charge and elutable functional moieties.
- Pharmaceutical Formulations and Process Engineering | Medical and Nano Biotechnology | Pharmaceutical Analysis and Bio Analytics | Bioinformatics and Computational Biology | Biomedical Signal Processing | Biomedical Engineering and Cancer
Location: 2
Session Introduction
Dan Liu
Patheon Inc., USA
Title: A case study for a Pharmaceutical Active Ingredient (API) manufacturing process in the USA
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.
Yongxiang Zhao
Guangxi Medical University, China
Title: A New Theranostic System Based on Endoglin Aptamer Conjugated Fluorescent Silica Nanoparticles
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.
Eunjoo Kim
Daegu Gyeongbuk Institute of Science and Technology (DGIST), Republic of Korea
Title: Reverse-expression of aging-related biomarkers by transfection of regulatory molecules via circulating system
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.
Claudia M. Rezende
Federal University of Rio de Janeiro, Brazil
Title: Effect of coffee diterpenes against Leishmania amazonesis
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.
Sangmun Shin
Dong-A University, Republic of Korea
Title: Comparative analysis of Quality by Design (QbD) platforms
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.