Vitamin E-Oligo(methyl diglycol L-glutamate) as a Biocompatible and Functional Surfactant for Facile Preparation of Active Tumor-Targeting PLGA Nanoparticles

作者：Wu, Jintian; Zhang, Jian; Deng, Chao^*; Meng, Fenghua; Zhong, Zhiyuan^*

来源：Biomacromolecules, 2016, 17(7): 2367-2374.

DOI：10.1021/acs.biomac.6b00380

• E TPGS
• POLYMERIC NANOPARTICLES
• CONTROLLED-RELEASE
• CO-DELIVERY
• DRUG
• DOXORUBICIN
• PACLITAXEL
• POLYPEPTIDE
• EMULSIFIER
• COPOLYMER

Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles have attracted an enormous interest for controlled drug delivery. Their clinical applications are, however, partly hindered by lack of biocompatible, biodegradable and functional surfactants. Here, we designed and developed a novel biocompatible surfactant based on amphiphilic vitamin E-oligo(methyl diglycol L-glutamate) (VEOEG) for facile fabrication of robust and tumor-targeting PLGA-based nanomedicines. VEOEG was prepared with controlled M-n of 1.7-2.6 kg/mol and low molecular weight distribution (D = 1.04-1.16) via polymerization of methyl diglycol L-glutamate N-carboxyanhydride using vitamin E-ethylenediamine derivative (VE-NH2) as an initiator. VEOEG had a hydrophile lipophile balance data of 13.8-16.1 and critical micellar concentration of 189.3-203.8 mg/L depending on lengths of oligopeptide. Using VEOEG as a surfactant, PLGA nanoparticles could be obtained via nanoprecipitation method with a small and uniform hydrodynamic size of 135 nm and positive surface charge of +26.6 mV, in accordance with presence of amino groups at the surface. The resulting PLGA nanoparticles could be readily coated with hyaluronic acid (HA) to form highly stable, small-sized (143 nm), monodisperse, and negatively charged nanoparticles (HA-PLGA NPs). Notably, paclitaxel-loaded HA-PLGA NPs (PTX-HA-PLGA NPs) exhibited better antitumor effects in CD44-positive MCF-7 breast tumor cells than Taxol (a clinical paclitaxel formulation). The in vivo pharmacokinetics assay in nude mice displayed that PTX-HA-PLGA NPs possessed a long plasma half-life of 3.14 h. The in vivo biodistribution studies revealed that PTX-HA-PLGA NPs had a high tumor PTX level of 8.4% ID/g, about 6 times better than that of Taxol. Interestingly, therapeutic studies showed that PTX-HA-PLGA NPs caused significantly more effective tumor growth inhibition, better survival rate and lower adverse effect than Taxol. VEOEG has emerged as a versatile and functional surfactant for the fabrication of advanced anticancer nanomedicines.

• 出版日期2016-7
• 单位苏州大学