Design, Development and Optimization of Carmustine-Loaded Freeze-Dried Nanoliposomal Formulation Using 32 Factorial Design Approach

Abstract

The objective of the current study was to develop and optimize a novel lyophilized liposomal formulation of anticancer agent carmustine, or bis-chloroethyl nitrosourea (BCNU) for prolonged release that could overcome the dose-dependent side effects and improve its bioavailability at the site of action. The optimization was done using a 3² factorial design approach wherein soya phosphatidylcholine (SPC) and cholesterol (CH) as independent variables. The optimized formulation (F4) exhibited high entrapment efficiency (81.57%) with an average vesicle size of 141.7 nm and a −22.6 mV Zeta potential. In-vitro drug release studies from all formulations revealed that the BCNU was released for up to 36 hours following the Higuchi matrix release model. The TEM, FTIR, DSC, PXRD, and SEM analyses confirm the formation of liposomes. BCNU-loaded nanoliposomal formulation demonstrated prolonged release, suggesting that it could be used to supplement cancer therapy efficiently with a reduction in dose-dependent side effects.