Journal
PHARMACEUTICAL RESEARCH
Volume 21, Issue 6, Pages 927-931Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1023/B:PHAM.0000029279.50733.55
Keywords
DNA vaccine; gene therapy; nanoparticles; polyester; transfection agent
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Purpose. The purpose of this study was the design of a polymeric platform for effective gene delivery using DNA-loaded nanoparticles. Methods. The polymers were synthesized by carbonyldiimidazole (CDI)-mediated coupling of diamines diethylaminopropylamine (DEAPA), dimethlyaminopropylamine (DMAPA) or diethylaminoethylamine (DEAEA) to poly(vinyl alcohol) (PVA) with subsequent grafting of D, L-lactide and glycolide (1: 1) in the stoichiometric ratios of 1: 10 and 1: 20 (free hydroxyl groups/monomer units). The polymers were characterized by H-1-NMR, gel permeation chromatography multiple-angle laser-light-scattering, and differential scanning calorimetry. DNA-loaded nanoparticles prepared by a modified solvent displacement method were characterized with regard to their zeta (zeta)-potential and size. The transfection efficiency was assessed with the plasmid DNA pCMV-luc in L929 mouse fibroblasts. Results. The polymers were composed of highly branched, biodegradable cationic polyesters exhibiting amphiphilic properties. The amine modification enhanced the rapid polymer degradation and resulted in the interaction with DNA during particle preparation. The nanoparticles exhibited positive zeta-potentials up to +42 mV and high transfection efficiencies, comparable to polyethlyenimine (PEI) 25kDa/DNA complexes at a nitrogen to phosphate ratio of 5. Conclusions. The polymers combined amine-functions and short poly(D, L-lactic-co-glycolic acid) ( PLGA) chains resulting in water-insoluble polymers capable of forming biodegradable DNA nanoparticles through coulombic interactions and polyester precipitation in aqueous medium. The high transfection efficiency was based on fast polymer degradation and the conservation of DNA bioactivity.
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