Nanoformulation of paclitaxel to enhance cancer therapy.

Abstract

Paclitaxel is a microtubule inhibitor causing mitotic arrest and is widely used in cancer chemotherapy. However, its poor water solubility restricts its direct clinical applications. In this article, we report paclitaxel-loaded nanoparticles that are water soluble and that can improve the drug's bio-distribution and therapeutic efficacy. Paclitaxel-loaded nanoparticles were synthesized by using Pluronic copolymers (F-68 and P-123) and surfactant (Span 40) as nanocarrier. The toxicity and cellular uptake of paclitaxel-loaded nanoparticles were evaluated. The paclitaxel-loaded nanoparticles can completely disperse into phosphate buffer saline to produce a clear aqueous suspension. Based on HPLC analysis, the drug-loading rate is 9.0 ± 0.1% while drug encapsulation efficiency is 99.0 ± 1.0%. The cytotoxicity assay was performed using breast cancer MCF-7 and cervical cancer Hela cells. For MCF-7 cells, the half maximal inhibitory concentrations (IC(50)) of paclitaxel-loaded nanoparticles and paclitaxel are 8.5 ± 0.3 and 14.0 ± 0.7 ng/mL at 48 hours and 3.5 ± 0.4 and 5.2 ± 0.5 ng/mL at 72 hours across several runs. IC(50) of paclitaxel-loaded nanoparticles and paclitaxel for Hela cells are 5.0 ± 0.3 and 8.0 ± 0.3 ng/mL at 48 hours and 2.0 ± 0.1 and 6.5 ± 0.3 ng/mL at 72 hours. In-vitro studies show that the drug's nanoformulation gives obvious enhancements in the drug's efficiency at killing cancer cells over paclitaxel alone. Materials of the nanocarrier used for nanoformulation are approved with low toxicity according to the result of cell studies. Conclusion: paclitaxel-loaded nanoparticles greatly improved the physicochemical properties of paclitaxel without modifying its chemical structure, allowing for deep-site cancer drug delivery and enhancing the drug therapeutic efficiency.