Abstract

Paclitaxel (PTX), as a broad spectrum and highly efficient antitumor drug, occupies an irreplaceable position in clinical cancer therapy. However, despite its definite therapeutic efficacy, its clinical application is largely limited by its extremely poor water solubility. Here, we report a facile method for encapsulating PTX into silk fibroin nanoparticles (PTX-SFNPs) using low molecular weight polyethylene glycol (L-PEG) as a solubilizer and high molecular weight polyethylene glycol (H-PEG) as an emulsifier and dehydrating agent, without adding any toxic organic solvents, surfactants, or other toxic agents. The efficiency at the volume of the reactor and processing time was 23.63 g/L, significantly higher than the desolvation method in ethanol and acetone. The PTX-SFNPs with a diameter of 100−300 nm exhibited promising drug loading (5.99 ± 0.28%) and encapsulation efficiency (30.91 ± 2.64%), excellent biocompatibility, and sustained drug release. In vivo studies using a mouse model with glioblastoma showed significant tumor inhibition without the systemic toxicity typical of traditional PTX formulations. Histological analysis confirmed the effective tumor penetration and biocompatibility of the nanoparticles. These findings suggest that PTX-SFNPs provide a promising approach for targeted glioblastoma therapy with the potential for future clinical applications.