Design of Amine-Modified Graft Polyesters for Effective Gene Delivery Using DNA-Loaded Nanoparticles

Abstract

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.

Methods for the Preparation and Manufacture of Polymeric Nanoparticles

“…In general, fragile molecules are better preserved from enzymatic degradation occurring in biological medium when they are entrapped in the nanocarrier (20,34). In this case, their association with the drug carrier should be done during the preparation of the nanocapsules or the nanospheres (19,20,(35)(36)(37)(38)(39). However, when the drug is highly susceptible to degradation which may occur during the preparation process of the drug carrier or when it does not associate during the preparation of the drug carrier, it can be loaded by adsorption on the surface of already prepared carriers (40)(41)(42).…”

Formulating Poly(Lactide-Co-Glycolide) Particles for Plasmid DNA Delivery

“…Transfection efficiency is increased in direct proportion to the amine substitution and inversely with the length of PLGA chain, which may be due to the proton sponge effect of the polymer or the hydrogel effect that leads to swelling of the polymer. 86,87 Other recently developed amine modified polymers that condense pDNA using similar principles include aminemodified PVA backbones grafted with PLGA. 88 Innovative approaches of combining the advantages of pegylation and cationic polymers include physically combining poly(ethylene glycol)-grafted chitosan with PLGA using a modified conventional emulsion solvent evaporation method.…”

Branched polyesters based on poly[vinyl-3-(dialkylamino)alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(d,l-lactide-co-glycolide): Effects of polymer structure on in vitro degradation behaviour

“…Modification of the branched structure with pendant amine functionalities led to positively charged biodegradable polyesters [11], which have successfully been used for the nanoencapsulation of DNA potentially useful for gene delivery system with surprisingly high transfection efficiency [12,13]. Polymereinsulin nanocomplexes for transmucosal protein delivery [14e16] and nanoparticles intended for pulmonary delivery of drugs [17e19] are further applications of this polymer class.…”