Synthesis, characterization, and formulation of poly-puerarin as a biodegradable and biosafe drug delivery platform for anti-cancer therapy

Abstract

Nano-drug delivery systems are widely used in medical diagnoses, tumour drug delivery and other fields due to their unique advantages. Thus, the preparation of more biocompatible nanocarriers by modifying natural materials has become a research hotspot in recent years. As a type of abundant and environment-friendly natural material, puerarin has been proven to be effective in the treatment of many diseases. However, its low solubility and low oral utilization limit its use. In this study, a novel biocompatible nanomaterial was developed. Puerarin was modified with an unsaturated olefin via acryloyl chloride and the amphiphilic polymer poly-puerarin was finally obtained through free radical polymerization, which was used in the preparation of a drug delivery system. Poly-puerarin nanoparticles (PPue NPs) were prepared by nanoprecipitation and used as a platform to load paclitaxel (PPue@PTX NPs). Physicochemical characterization showed that the nanoparticle size was around 70 nm and the drug loading efficiency of PTX was up to 23.8%. The cytotoxicity test revealed that the modified puerarin derivatives, PPue, exhibited good biocompatibility even at large doses of 100 μg mL⁻¹ and the PPue@PTX NPs still maintained the excellent anti-cancer effect of PTX. The in vitro cellular uptake assay demonstrated that the PPue@PTX NPs were rapidly uptaken by CT26 cells. In the in vivo experiments, the PPue@PTX NPs featured rapid aggregation and slow clearance and the most significant effect of inhibiting tumour growth among all the treatment groups. Therefore, our work provides a new strategy for the modification of natural drugs and PPue is expected to become a new safe and reliable nano-drug delivery platform.