Pegylation of Nanoliposomal Paclitaxel Enhances its Efficacy in Breast Cancer

Purpose: To encapsulate paclitaxel into nanoliposomes, followed by pegylatation, in order to improve its therapeutic index and reduce side effects in breast cancer.
Methods: In order to prepare nanoliposomal paclitaxel, varying ratios of phosphatidylcholine, cholesterol and paclitaxel were mixed and the formulations pegylated with poly-ethylene glycol 2000 (PEG 2000) to enhance stability, efficiency, as well as solubility. The mean diameter of nanoliposomal paclitaxel and pegylated nanoliposomal paclitaxel were measured by Zeta sizer device and release of paclitaxel from both formulations was determined within 28 h by dialysis method. The cytotoxicity of nanoliposomal and pegylated nanoliposomal paclitaxel was evaluated using 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay.
Results: The mean diameter of nanoliposomal paclitaxel and pegylated nanoliposomal paclitaxel was 421.4 and 369.1 nm, respectively, while encapsulation efficiency was 91.3 ± 5.7 and 95.2 ± 6.3 %, respectively. Paclitaxel released from both formulations in 28 h was 5.53 and 5.02 %, respectively. The cytotoxicity of pegylated nanoliposomal paclitaxel was significantly (p <0.05) greater than that of nanoliposomal paclitaxel (their IC₅₀ = 79.8±2.9 and 86.25±3.4 µg/ml, respectively).
Conclusion: The release pattern and cytotoxicity of pegylated nanoliposomal paclitaxel show that the formulation is superior to nanoliposomal paclitaxel. Furthermore, the mean particle size of pegylated nanoliposome is smaller than that of the non-pegylated preparation.

Keywords
Paclitaxel; Nanoliposome; Breast cancer; Pegylation; Drug delivery; Cytotoxicity