Co-delivery of carboplatin and paclitaxel via cross-linked multilamellar liposomes for ovarian cancer treatment

Abstract

Carboplatin (CPT) and paclitaxel (PTX) used in combination is one of the most effective treatments for ovarian cancer. However, the traditional combination methods used to co-administrate CPT and PTX showed limited clinical efficacy due to their distinct pharmacokinetics. Although much effort has been devoted to developing nanoparticles capable of encapsulating drugs with different lipophilicites, co-delivery of carboplatin with paclitaxel by a single nanoparticle has rarely been reported. Here, we encapsulated and delivered this drug combination to ovarian cancer cells at a controlled ratio by a previously reported crosslinked multilamellar liposome vesicle (cMLV). A 1 : 1 CPT/PTX molar ratio for cMLVs (CPT/PTX) combination treatment was found to induce the strongest anti-tumor synergism and to target ALDH+ cancer stem cells (CSC) in vitro. Moreover, we demonstrated that this co-encapsulation strategy reduced systemic cytotoxicity and resulted in a stronger anti-tumor effect when compared to free drug combinations and individual drug-loaded cMLVs in an OVCAR8 ovarian cancer xenograft mouse model. Thus, this study suggests a potentially promising combination therapy for ovarian cancer in clinical practice.