Development of sheath-core biodegradable nanofibers for peptide delivery
| Autor: | Yu Ling Hsieh, 謝玉玲 |
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| Rok vydání: | 2017 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 105 This work develops two types of sheath-core structured drug-eluting nanofibers, namely insulin/ticargrelor and insulin/vildagliptin nanofibers. To prepare the biodegradable insulin/ticargrelor membranes, poly-D-L-lactide-glycolide (PLGA) and ticagrelor were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) respectively. The solutions were then coaxially electrospun into insulin/ticargrelor sheath-core structured nanofibrous tubes, which were mounted onto commercially available bare-metal stents. The in vitro release rates of the pharmaceuticals from the nanofibers were determined using an elution method and a high-performance liquid chromatography assay. The experimental results thus obtained suggest that the biodegradable nanofibers released high concentrations of ticagrelor for more than three weeks. The effectiveness of the local delivery of ticagrelor in reducing platelets was studied. The proposed hybrid stent/biodegradable ticagrelor-loaded nanofibers contributed substantially to the local and sustainable delivery of a high concentration of drugs to promote re-endothelialization, improve endothelial function, reduce inflammatory reaction, and inhibit neointimal formation of the injured artery. Meanwhile, biodegradable nanofibrous drug-eluting membranes were also developed to provide sustained release of vildagliptin for repairing wounds associated with diabetes. To prepare the biodegradable membranes, poly-D-L-lactide-glycolide (PLGA) and vildagliptin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and then spun into nanofibers by coaxial electrospinning. An elution method and an HPLC assay were utilized to characterize the in vivo and in vitro release rates of the pharmaceuticals from the membranes. The biodegradable nanofibrous membranes released high concentrations of vildagliptin for more than four weeks. Moreover, nanofibrous vildagliptin-eluting PLGA membranes were more hydrophilic and had a greater water-containing capacity than virgin PLGA fibers. The membranes also improved wound healing and re-epithelialization in diabetic rats relative to the control. The experimental results in this work suggest that nanofibrous vildagliptin-eluting membranes were functionally active in the treatment of diabetic wounds and very effective as accelerators in the early. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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