Browsing by Subject "Medical Biotechnology"
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Item Advanced Problem Solving in the Biotherapeutics Industry: Parameters influencing the delivery of a novel cell therapy product and exploration of a new method for determining activity of Clostridium histolyticum collagenase, a wound debridement enzyme(2015-05-01) Harris, Melanie A.; Jerry W. Simecka; Patricia A. GwirtzBiotechnology is a multi-faceted industry with many unique challenges that require knowledge in a broad range of topics. When working in the wound care field it is necessary to not only create a product in the laboratory, but also effectively bring it to the patient. This task requires many skilled people who can test it for efficacy, design and conduct clinical trials, confirm quality and consistency, design packaging, consider transportation issues and so on. The following investigation focuses on the testing of a cellular product and its accompanying device under various conditions as well as the exploration of a new assay capable of the activity of a wound debridement enzyme. The results of the product/device testing have generally confirmed the comparability of the cellular product devices as well as their resistance to various temperatures encountered in the clinical environment. A new modified assay for the testing of collagenase has been established as precise and comparable to current methods, though it requires more testing to confirm robustness.Item Creating novel purification and biochemical characterization protocols for C. collagenase from Clostridium histolyticum, developing a new emergency medicine product, and formulating several novel therapies for chronic and acute wound treatment(2017-05-01) Mars, Jason P.; Jerry W. Simecka; Patricia A. Gwirtz; Aleksa JovanovicThe pharmaceutical industry not only includes infinite areas of specialization, but also consists of distinct areas that do not typically overlap. Biotechnology is the branch of medicinal research that bridges the gap between the fields within the pharmaceutical industry by being able to take on the challenges that require knowledge of a vast range of information. This practicum was organized to put the scientific knowledge and the interdisciplinary practices of biotechnology to use in a modern day, pharmaceutical company specializing in wound therapy and skincare: Smith & Nephew Biotherapeutics. Wound therapy has the widest range of application due to being one of the few fields that affects everyone, regardless of medical disposition. The specific goals of this practicum were: to develop novel purification and biochemical characterization protocols for C. collagenase from Clostridium histolyticum to replace current production methods of Santyl®, to develop a working prototype of a venom-based, hemostatic film, and perform reformulation, quality control, troubleshooting, and verification testing on samples of Regranex®, Iodosorb “Max”, and EU-Collagenase. Every goal presented was approached with the end results of saving Smith & Nephew costs, reducing bioburden of production, and creating more efficient protocols to bring Smith & Nephew into the modern age.Item Targeted Nanoparticles for the Treatment of Neuroblastoma(2011-05-01) Pratap, Suraj; Lacko, Andras G.Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants and children. However, the mechanism by which it is initiated and subsequently develops on the molecular and cellular level is yet to be fully elucidated. Its wide spectrum of clinical presentation has baffled physicians and biomedical scientists alike. The variant called high risk neuroblastoma (HRNB) is extremely resistant to the currently available drug regimes. Despite the recent advances in anti-cancer agents and the use of multi-modality therapy for the treatment of HRNB the morbidity and mortality in this group of patients continues to remain high. The purpose of our project was to find novel alternative therapeutic approaches by encapsulating known anti-NB agents in a lipoprotein based formulation to achieve selected, targeted delivery of these drugs to HRNB tumors. We wanted to enhance the therapeutic efficacy of these drugs that have shown encouraging results in pre-clinical trials but have so far exhibited an adverse pharmacokinetic profile precluding their systemic application. Our laboratory has been working for the last several years on a novel drug delivery platform by encapsulating drugs into the core of high density lipoprotein (HDL) type nano-particles. Using this strategy, we encapsulated all-trans retinoic acid (ATRA), fenretinide (FR) and valrubicin into reconstituted HDL (rHDL) nanoparticles and subsequently evaluated some of their physical and chemical properties and their anti-NB potential. Further, we tested the efficiency of an apolipoprotein mimetic peptide called 5-A peptide as a component of rHDL particles and compared its efficiency with apolipoprotein A-1 (Apo-A1). The 5-A peptide offers numerous advantages over the Apo-A-1 both in terms of cost of production as well as manufacturing time. After successfully encapsulating the drugs, we characterized them and tested their cytotoxic potential on various cancerous cell lines. We also conducted cell uptake studies to test our hypothesis of tissue targeting and selective uptake of rHDL nano-particles mediated by the scavenger receptor type B1 (SR-B1). We conducted a pilot study on nude mice in which we administered rHDL containing fluorescent dye intravenously in mice xenografted with NB tumors and took subsequent images to track its distribution in the body. Our results demonstrate that it is possible to encapsulate ATRA, FR and valrubicin into rHDL preparations with a predictable efficiency; these nano-particles show a dose dependent cytotoxic effect on NB cell lines. We anticipate that the results of our studies will facilitate the application of liposomal nano-particles and these novel drugs in the treatment of HRNB in the future.Item The Effect of Lymphatic Pump Treatment on Anti-Tumor Immune Responses(2011-05-01) McCauley, Lyndsey R.; Hodge, Lisa M.The lymphatic system’s significance in maintaining health has been focused on by the osteopathic medical profession for years. Osteopathic manipulative treatments (OMT), specifically lymphatic pump techniques (LPT), aim at increasing lymphatic circulation and improving the clearance of interstitial fluid, inflammatory agents, and protein from the interstitial space. However, certain osteopathic manipulative techniques, such as LPT, are contraindicated in the presence of cancer with metastatic potential because it is thought that by accelerating the flow of lymph through the lymphatic vessels, tumor cells may metastasize throughout the body via the lymphatics. However, this theory lacks scientific proof. Studies previously conducted by our lab show that LPT increases thoracic duct lymph flow and leukocyte numbers in the rat and significantly decreases solid tumor formation and increases leukocyte concentrations in the lungs of rats with tumors (unpublished data). It is possible that increased lymph flow along with an increased number of circulating leukocytes can improve immune surveillance, providing recognition of and protection against pathogens and disease. Therefore, we hypothesized that administration of LPT would enhance anti-tumor immune responses in the lungs of rats with pulmonary tumors. In order to test this hypothesis, this thesis focused on one specific aim: to determine if LPT enhances leukocyte activation and/or function, thereby enhancing anti-tumor activities, such as tumor lysis and cytokine secretion.