pH-triggered liposomal strategy for cisplatin in lung cancer therapy

Abstract

Cisplatin (Cis) is the first-line chemotherapy for treating the non-small-cell lung cancer. However, its low solubility, low bioavailability, and potential side effects limit its use. To overcome these drawbacks, novel pH-sensitive liposomal Cis formulations have been developed using a rapid and practical ethanol injection technique. In this study, two different liposome types were prepared, one based on phosphatidylcholine and cholesteryl hemisuccinate (CHEMS), the other containing 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in combination with CHEMS. Their homogeneity, smaller particle sizes (< 200 nm) and drug integration were confirmed using the DLS method and FT-IR and SEM-EDS, respectively. The loading efficiency was changed from 35 to 50% depending on the composition. In vitro drug release studies showed a minimum release at physiological pH (7.4) and a significantly increased release at acidic pH (5.5), in particularly for DOPE liposomes, indicating the higher pH-sensitivity. Cytotoxicity analyses performed in A549 lung cancer cell line showed that both liposomal formulations exhibited stronger antitumour effects compared to free Cis. This effect was supported by increased apoptotic activity confirmed by Annexin-V/PI staining method. These findings suggest that the pH-sensitive liposomes developed in this study offer a promising and scalable approach to enhance the selective delivery and therapeutic efficacy of Cis.