Tuning ligand number to enhance selectivity of paclitaxel liposomes towards ovarian cancer

Abstract

Although several anticancer drugs are currently available to tackle the growing menace of cancer, their efficacy is severely hampered due to their non-selectivity and associated toxicity to the healthy cells. The prime hurdles in the fabrication of efficient and targeted cancer therapy are improving the selectivity of these drugs towards cancerous cells while reducing their toxicity to the healthy cells. Thus, the current study aims to develop a liposomal system with an optimized number of folate moiety anchored on its surface (480/liposome) to selectively target the ovarian tumor cells in vivo. The pharmacokinetics of the folate anchored liposome indicated a 16.61-fold increase in the area under the curve along with an increased mean retention time of 12.41 h, as compared to the marketed formulation. In vivo biochemical assays indicated a significant reduction in reactive oxygen species generation, which could ultimately lead to a decrease in tumor incidence. Antitumor efficacy study on an ovarian tumor model showed an improved targeting potential of the optimized liposome with a 6.7-fold reduction in tumor volume and 1.56-fold reduction in tumor weight compared to the marketed formulation. This was achieved along with more than 75% survival without any significant drop in body weight. The findings collectively suggest the potential of rationalizing and optimizing the ligand number anchored on the liposomal surface can help in explicitly targeting the ovarian tumor in vivo. Thus, optimizing the ligand number could serve as an important protocol for designing target-based delivery systems concerning targeting ligands.