Global ETD Search

1	Developing a Minimally Invasive Sustained Release System for Glioma Therapy Kao, Chen-Yu 16 November 2007 (has links) Malignant brain tumor is one of the most lethal forms of cancers. In the United States alone, approximately 20,500 new cases of primary malignant brain and central nervous system tumors are expected to be diagnosed in 2007 with 12,740 deaths estimated. Treatment of malignant brain tumor remains a major challenge despite recent advance in surgery and other adjuvant therapies, such as chemotherapy. The failure of potential effective chemotherapeutics for brain tumor treatment is usually not due to the lack of potency of the drug, but rather can be attributed to lack of therapeutic strategies capable of overcoming blood brain barrier for effective delivery of drug to the brain tumor. In this thesis, we developed a minimally invasive sustained release system for glioma therapy. The present study was initiated in an effort to incorporated Doxorubicin (DOX) loaded PLGA particle into an agarose gel, which can provide a continuous release of DOX locally to the tumor site. DOX, a toposiomearase II inhibitor, is not currently used clinically for brain tumor treatment because when delivered systemically it does not cross BBB. Our hydrogel particle system can overcome this shortcoming of DOX. The results from this study demonstrate that the DOX/PLGA particle gel system can maintain the bioactivity of DOX and sustained release DOX for at least 15 day in vitro. The result of in vivo study showed the DOX/PLGA particle gel treated group had significantly extend the medium survival of 9L glioma bearing rat from 21 days to 29 days. Therefore, the success experience of this local and sustained delivery device might benefit the development of future glioma therapy strategy. BBB Hydrogel Local sustained delivery PLGA Doxorubicin Gliomas Intracranial tumors Blood-brain barrier Controlled release technology Doxorubicin
2	Reduced Burst Release of Bioactive rhBMP-2 from a Three-phase Composite Scaffold Grant, David William 31 December 2010 (has links) Recombinant human bone morphogenic proteins (rhBMPs) are extensively studied and employed clinically for treatment of various bone defects. Current clinical delivery vehicles suffer wasteful burst releases that mandate supra-physiological dosing driving concerns over safety and cost. It was therefore investigated whether a unique drug delivery vehicle sequestered within a composite scaffold could lower the burst release of rhBMP-2. PLGA-calcium phosphate tri-phasic composite scaffolds delivered model protein BSA with burst release of ~13% and sustained kinetics of 0.5-1.5% BSA/day up to 45 days. rhBMP-2 was delivered with zero burst release however at much lower levels, totaling 0.09% to 0.9 % release over 10 days, but had up to 6.3-fold greater bioactivity than fresh rhBMP-2 (p<0.05). In conclusion, the three-phase composite scaffold can deliver bioactive proteins with a reduced burst release and sustained secondary kinetics. Drug delivery Bone Bone morphogenic protein BMP BMP-2 rhBMP-2 bone graft tissue engineering scaffold bone tissue engineering regenerative medicine osteoinduction osteoconduction osteogenesis generative surgery autoraft replacement synthetic autograft replacement morphogenic bioactivity assay protein release kinetics bovine serum albumin model protein biomaterials biomaterial surface analysis scanning electron microscope application accelerating voltage application burst release sustained kinetics sustained delivery composite scaffold three phase scaffold PLGA calcium phosphate mineral-polymer composite sterilization BMP sterilization long-term storage BMP storage 0541
3	Reduced Burst Release of Bioactive rhBMP-2 from a Three-phase Composite Scaffold Grant, David William 31 December 2010 (has links) Recombinant human bone morphogenic proteins (rhBMPs) are extensively studied and employed clinically for treatment of various bone defects. Current clinical delivery vehicles suffer wasteful burst releases that mandate supra-physiological dosing driving concerns over safety and cost. It was therefore investigated whether a unique drug delivery vehicle sequestered within a composite scaffold could lower the burst release of rhBMP-2. PLGA-calcium phosphate tri-phasic composite scaffolds delivered model protein BSA with burst release of ~13% and sustained kinetics of 0.5-1.5% BSA/day up to 45 days. rhBMP-2 was delivered with zero burst release however at much lower levels, totaling 0.09% to 0.9 % release over 10 days, but had up to 6.3-fold greater bioactivity than fresh rhBMP-2 (p<0.05). In conclusion, the three-phase composite scaffold can deliver bioactive proteins with a reduced burst release and sustained secondary kinetics. Drug delivery Bone Bone morphogenic protein BMP BMP-2 rhBMP-2 bone graft tissue engineering scaffold bone tissue engineering regenerative medicine osteoinduction osteoconduction osteogenesis generative surgery autoraft replacement synthetic autograft replacement morphogenic bioactivity assay protein release kinetics bovine serum albumin model protein biomaterials biomaterial surface analysis scanning electron microscope application accelerating voltage application burst release sustained kinetics sustained delivery composite scaffold three phase scaffold PLGA calcium phosphate mineral-polymer composite sterilization BMP sterilization long-term storage BMP storage 0541

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