A dual-targeted liposomal doxorubicin formulation achieved 6.9-fold greater tumour drug accumulation and an 80% reduction in cardiac drug exposure relative to free doxorubicin.
Does dual-targeted liposomal doxorubicin improve therapeutic efficacy and reduce cardiac exposure compared to free doxorubicin in preclinical models?
Dual-targeted liposomal doxorubicin significantly improves tumor accumulation and reduces cardiac exposure in preclinical models, suggesting a safer chemotherapy profile with reduced cardiotoxicity.
The Conventional intravenous Doxorubicin Hydrochloride (DOX) chemotherapy remains constrained by dose-limiting cardiotoxicity and multidrug-resistance-mediated efflux, while first-generation passive liposomal formulations (e.g., DOXIL) depend on the heterogeneous Enhanced Permeability and Retention (EPR) effect for tumour accumulation. This study aimed to formulate and evaluate a dual-targeted — passive (PEGylated stealth) plus active receptor-mediated — liposomal DOX nanomedicine for intravenous infusion with enhanced therapeutic efficacy. Liposomes composed of HSPC, cholesterol and DSPE-PEG2000 were prepared by thin-film hydration and extrusion, surface-functionalised with hyaluronic acid via EDC/NHS conjugation for CD44-receptor targeting, and loaded with DOX by the ammonium-sulphate pH-gradient remote-loading method. The optimised formulation showed a mean particle size of 98.5 ± 1.1 nm, PDI of 0.12 ± 0.03, zeta potential of −3.2 ± 0.5 mV, and encapsulation efficiency of 97.8% ± 1.0%. In vitro, targeted liposomes exhibited an 11.8-fold lower IC50 than non-targeted liposomes and a 3.0-fold lower IC50 than free DOX in receptor-positive A549 cells, with receptor-blocking studies confirming ligand-specific uptake. In vivo, the targeted formulation achieved a 68-fold longer circulating half-life, an 18-fold higher AUC, 6.9-fold greater tumour drug accumulation, and an approximately 80% reduction in cardiac drug exposure relative to free DOX. These results demonstrate that combining passive EPR-based accumulation with active receptor-mediated targeting substantially widens the therapeutic index of Doxorubicin Hydrochloride, supporting its potential as a safer, more effective nanomedicine platform for cancer chemotherapy.
University et al. (Sun,) conducted a other in Cancer. Dual-targeted liposomal Doxorubicin Hydrochloride vs. Free Doxorubicin and non-targeted liposomes was evaluated. A dual-targeted liposomal doxorubicin formulation achieved 6.9-fold greater tumour drug accumulation and an 80% reduction in cardiac drug exposure relative to free doxorubicin.