Development and Characterization of Docetaxel Encapsulated pH-Sensitive Liposomes for Cancer Therapy

The present study investigates the formulation of pH-sensitive liposomes of docetaxel prepared by TFH technique using membrane composition consisting of one or combination of lipids such as DOPE, HSPC, CHOL, CHEMS and Cholesterol. Optimized process parameters evaluated are composition of solvent system (CHCl3:MeOH) (2:1), vacuum applied (600mmHg), solvent evaporation time (60 min), speed of rotation (100 rpm), hydration time (60 min), hydration volume (2 ml), no. of sonication cycles (30 sec) [(3 cycles (80% amp, 0.6 cycle)]. Optimized formulation parameters evaluated are Drug: Lipid ratio (1:20), hydration media (HEPES buffer pH 8.2), LIPID: CHOL ratio (8:2), LIPID: CHOL: CHEMS (6:2:2), HSPC: DOPE (1:3). The particle size of optimized formulation was found to be 111.0 nm ± 2.713nm with PDI of 0.227. Zeta potential of optimized formulation was -22.8 mV, attributed to the anionic nature of lipid. Percentage entrapment efficiency of optimized liposomal formulation was 64.79±0.230. Based on the DSC study of lyophilized docetaxel loaded liposome, melting endotherm for docetaxel was not observed, which indicates that docetaxel in the liposome was in an amorphous or disorderedcrystalline phase of molecular dispersion or a solid state in the lipid layer of liposome. The surface morphology of lyophilized pH-sensitive liposomes exhibits a spherical shape of liposome. For preparing dry solid liposomal formulation, Trehalose was found more effective cryoprotectant showing highest PDR (92.76±0.571) and better size (173.4±3.721). From the In vitro diffusion study, it was concluded that the pH-sensitive liposomes shows higher pH-sensitivity since it release more amount of drug at pH 5.0. The cytotoxicity of docetaxel in conventional and pH-sensitive liposome on lung cancer cells, A549, was compared with that plain docetaxel by MTT assay. The higher cytotoxicity of pH-sensitive liposome than that of conventional liposome and plain drug was found mainly due to increase in the intracellular release of the drug from the pH-sensitive liposome at endosomal pH and avoiding the lysosomal degradation of the drug.