An acid-labile temperature-responsive sol-gel reversible polymer for enhanced gene delivery to the myocardium and skeletal muscle cells

Abstract

The work demonstrates the development of acid-labile temperature-responsive sol-gel reversible polymer for enhanced in vivo myocardium and skeletal muscle gene delivery. In this report, multi-block copolymers (MBCPs) synthesized from pluronic (R) and di-(ethylene glycol) divinyl ether (DEGDVE) were used as a delivery vehicle for controlled and sustained release of plasmid DNA (pDNA) in in vitro as well as in vivo experiments. The non-ionic MBCP/pDNA complex showed remarkable transfection efficiencies against the myocardium cells as well as muscle cells in vivo, which is otherwise very difficult to achieve by using cationic polymers. In in vitro experimental settings, this intelligent stimuli-responsive polymer is shown to improve the transfection efficiency of branched polyethylenimine (BPEI)/pDNA complex when used together. The effect of MBCP on the surface charge and particle size of its various complexes with pDNA and BPEI was also studied. The release profile of pDNA from the MBCP gel was investigated and pH of the degraded polymer was also monitored to ascertain its non-cytotoxicity arising due to the increased acidity as observed with other PLGA-based polymers. The rapid sol-gel transition of MBCP under thermal stimuli with concomitant release of pDNA under acidic stimulation has potential for site specific, efficient and controlled transfection of therapeutic gene. In short, MBCP provides the silver lining in combat against the hurdles encountered in transfection to myocardial or other muscle cells. (C) 2009 Elsevier Ltd. All rights reserved.