Comparative Assessment of Active Targeted Redox Sensitive Polymersomes Based on pPEGMA-S-S-PLA Diblock Copolymer with Marketed Nanoformulation

摘要

In the present work, polymersomes based on self assembled, folate-targeted, redox-responsive, ATRP-based amphiphilic diblock copolymer poly(polyethylene glycol)-S-S-polylactide with disulfide linkage were developed for efficient doxorubicin (DOX) delivery and compared with marketed DOXIL nano formulation. The polymersomes formulation was optimized by quality by design approach providing monodisperse nanostructures of similar to 110 nm and enhanced DOX loading of similar to 20%. Polymersomes showed excellent stability as per the ICH guidelines over the extended storage period of 3 months. The in vitro drug release profile confirmed the redox sensitive behavior of polymersomes providing 80% drug release in endosomal pH 5 with 10 mmol GSH as compared to similar to 20% release at pH 7.4. The targeted polymersomes achieved enhanced cellular internalization in folate receptor overexpressing cell lines, MDA-MB-231 and HeLa, providing similar to 24% higher tumor reduction than DOXIL in Ehrlich ascites tumor bearing Swiss albino mice.