4.4 Article

Development of novel biodegradable polymeric nanoparticles-in-microsphere formulation for local plasmid DNA delivery in the gastrointestinal tract

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AAPS PHARMSCITECH
卷 9, 期 1, 页码 288-294

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SPRINGER
DOI: 10.1208/s12249-007-9021-9

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gene delivery; GI tract; NiMOS; non-viral; transfection

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There is a critical need for development of novel delivery systems to facilitate the translation of nucleic acid-based macromolecules into clinically-viable therapies. The aim of this investigation was to develop and evaluate a novel nanoparticles-in-microsphere oral system (NiMOS) for gene delivery and transfection in specific regions of the gastrointestinal (GI) tract. Plasmid DNA, encoding for the enhanced green fluorescent protein (EGFP-N1), was encapsulated in type B gelatin nanoparticles. NiMOS were prepared by further protecting the DNA-loaded nanoparticles in a poly(epsilon-caprolactone) (PCL) matrix to form microspheres of less than 5.0 mu m in diameter. In order to evaluate the biodistribution following oral administration, radiolabeled (In-111-labeled) gelatin nanoparticles and NiMOS were administered orally to fasted Balb/C mice. The results of biodistribution studies showed that, while gelatin nanoparticles traversed through the GI tract fairly quickly with more than 54% of the administered dose per gram localizing in the large intestine at the end of 2 h, NiMOS resided in the stomach and small intestine for relatively longer duration. Following oral administration of EGFP-N1 plasmid DNA at 100 mu g dose in the control and test formulations, the quantitative and qualitative results presented in this study provide the necessary evidence for transfection potential of NiMOS upon oral administration. After 5 days post-administration, transgene expression in the small and large intestine of mice was observed. Based on these results, NiMOS show significant potential as novel gene delivery vehicle for therapeutic and vaccination purposes.

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