Paclitaxel Loaded Hyaluronic Acid Polymerized Nanoparticles Designed for Ovarian Cancer Therapy

Abstract

We aimed to develop an ovarian cancer-directed drug delivery system based on the high affinity of hyaluronic acid for CD44. The effects and mechanisms of hyaluronic acid-containing nanoparticles were investigated. The expression of CD44 in ovarian cancer was also determined. Hyaluronic acid polymerized nanoparticles (HANPs), FITC-HANPs, and paclitaxel (PTX)-HANPs were prepared, and their characteristics were evaluated. The in vitro targetability and cytotoxicity properties of PTX-HANPs were evaluated through in vitro drug uptake and cytotoxicity assays. The mechanisms of PTX-HANPs activity were investigated by apoptosis, wound healing, and Transwell invasion assays. In vivo targeting properties of HANPs were observed using a mouse ID8 subcutaneous model. in vitro experiments revealed an improved uptake of FITC-HANPs. The cytotoxicity of PTX-HANPs in A2780/CP70 and ID8 cells was higher than that of PTX alone. PTX-HANPs increased cell apoptosis in a dose-dependent manner and exhibited a similar ability as PTX to inhibit cell migration. Furthermore, HANPs did not promote A2780/CP70 or ID8 cell migration and showed limited inhibitory effects on their invasion. In vivo drug tracing experiments demonstrated the targetability of FITC-HANPs. In conclusion, PTX-HANPs improved PTX targetability and exhibited potent tumor-specific therapeutic activities. It may be considered a promising formulation for the preclinical development of agents targeting epithelial ovarian cancer.