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ȣ - 530547 204 |
Evaluation of the Efficacy of eNOS Gene Therapy using Poly(lactic-co-glycolic acid) Nanosphere in Spontaneous Hypertensive Rat. |
충북대학교 의과대학 내과학교실 순환기내과 |
심태진, 박노관, 최은주, 박건재, 김연정, 이상엽, 배장환, 황경국, 김동운, 조명찬 |
Background and Objectives: Poly(lactic-co-glycolic acid) (PLGA) has been studied for many years as a suitable drug delivery material, mainly due to its chemical biocompatibility, total biodegradability, and non-toxic degradation products. The aim of this study was to evaluate the effects of plasmid eNOS-loaded PLGA nanospheres as a gene delivery system to control the high blood pressure. Methods: Plasmid DNA was conjugated to PLGA, which was formulated into nanoparticle via double emulsification-solvent evaporation method. For physicochemical characterization, the particle size and zeta potential was measured by photon-correlation spectroscopy (PCS). In vitro, releases of plasmid DNA from PLGA nanospheres were performed in phosphate buffered saline. In vivo, PLGA/pDNA nanosphere with eNOS or GFP gene (10μg/100μL) was injected intravenous to SHR on beginning and 10 days after. Blood pressure (BP) was measured by tail cuff method for 5 weeks. Results: The average size of PLGA nanospheres prepared to 424 nm (Fig.), and DNA loading efficiency within PLGA nanospheres were about 21%. During study period, eNOS/PLGA group showed reduced BP than control group (Fig.). Urine nitric oxide concentration was increased from eNOS/PLGA group than control. Conclusion: In this study, we made the optimal condition to prepare PLGA nanosphere as a non-viral gene delivering system. With this, we can control BP effectively in animal hypertension model.
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