Lipoic Acid-derived Cross-linked Liposomes for Reduction-responsive Delivery of Anticancer Drug

In this study, a novel disulfide cross-linked liposomes (CLs) assembled from dimeric lipoic acid-derived glycerophosphorylcholine (di-LA-PC) conjugate was developed. The conjugate was synthesized by a facial esterification of lipoic acid (LA) and glycerophosphorylcholine (GPC) and characterized by MS, 1H NMR and 13C NMR. Featuring the enhanced serum-stability and intracellular drug release determined by in vitro stability and GSH-responsive behavior, CLs prepared with dried thin film technique following 10 mol.% DTT cross-linking can attain effective delivery of anticancer candidates. Notably, CLs stably encapsulated doxorubicin (Dox) in their vesicular structures and showed a remarkable thiol-sensitive release of payload upon cellular uptake by cancer cells, compared to that of uncross-linked liposomes (uCLs) or Doxil-like liposome (DLLs). The cell viability and apoptosis of Dox-loaded CLs worked the pronounced cytotoxic effects to MCF-7 cells with an IC50 value of 10.8 μg Dox equiv./mL comparable to free Dox and 2.8-fold higher than DLLs. More importantly, it is demonstrated that the nanoscale characteristics of Dox-loaded CLs could prevent the proliferation of adriamycin-resistant MCF-7/ADR cell line, highlighting their potential in reversal of drug resistance. Furthermore, the preliminary in vivo test (n=3) showed that disulfide cross-linked liposomal formulation of Dox (Dox-CLs) improved the therapeutic efficacy compared to free Dox and DLLs in a human breast carcinoma ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research