A New Type of Nanogel Carrier based on Mixed Pluronic Loaded with Low-Dose Antitumor Drugs

Abstract

To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography (HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic® F-127, which binds folic acid (FA), Pluronic® F-68 and triptolide (TPL) (FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer (FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy (AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant (MDR) breast cancer cells (MCF-7/ADR cells) and induce cell death. The effects were signifcantly different from those of free TPL (P < 0.01). Using the fuorescent probe Nile red (Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FA-F-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma (HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr (P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property, targeted tumor cells, and could improve the antitumor effects of TPL; hence, they are ideal carriers for low-dose antineoplastic drugs.