Abstract
Non-viral polymeric gene delivery systems offer increased protection from nuclease degradation, enhanced plasmid DNA (pDNA) uptake, and controlled dosing to sustain the duration of pDNA action. Such gene delivery systems can be formulated from biocompatible and biodegradable polymers such as poly( d, l-lactic-co-glycolic) acid (PLGA). Experimental loading of hydrophilic macromolecules such as pDNA is low in polymeric particles. The study purpose was to develop a supercritical fluid extraction of emulsions (SFEE) process based on CO 2 for preparing pEGFP-PLGA nanoparticles with high plasmid loading and loading efficiency. Another objective was to determine the efficacy of pFlt23k, an anti-angiogenic pDNA capable of inhibiting vascular endothelial growth factor (VEGF) secretion, following nanoparticle formation using the SFEE process. Results indicated that the SFEE process allows high actual loading of pDNA (19.7%, w/w), high loading efficiency (>98%), and low residual solvents (<50 ppm), due to rapid particle formation from efficient solvent removal provided by the SFEE process. pFlt23K-PLGA nanoparticles were capable of in vitro transfection, significantly reducing secreted VEGF from human lung alveolar epithelial cells (A549) under normoxic and hypoxic conditions. pFlt23K-PLGA nanoparticles did not exhibit cytotoxicity and are of potential value in treating neovascular disorders wherein VEGF levels are elevated.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.