Superior antitumor effect of extremely high drug loading self-assembled paclitaxel nanofibers

Publication date: 30 June 2017 Source:International Journal of Pharmaceutics, Volume 526, Issues 1–2 Author(s): Huae Xu, Xiaowei Lu, Jun Li, Dan Ding, Hong Wang, Xiaolin Li, Weiping Xie Recent studies focused on the nanodelivery system of paclitaxel (Ptx) to overcome the poor solubility and hypersensitivity of Ptx caused by the application of Cremophor EL as a solvent. Although many studies use different types of polymers as carriers to prepare Ptx-loaded polymeric nanoparticles, the relatively low loading efficiency of Ptx-loaded polymeric nanoparticles significantly limits its application. Here, we design and synthesize a simple conjugation of Ptx and succinic acid (Ptx-SA), which can self-assemble into nanofibers and become “carrier-free” with Ptx as the drug carrier. The highest loading efficiency of Ptx is 89.5% with a controlled release pattern. The cellular uptake study indicates the internalization of Ptx-SA nanofibers by A549 cells. The in vitro cytotoxicity test results indicate that Ptx-SA nanofibers were much more effective in inhibiting the proliferation of A549 cells than free Ptx, particularly at the lower working concentration. The clonogenic assay shows the enhanced effect of Ptx-SA in ameliorating the clonogenic abilities of A549 cells compared with the equivalent dose of free Ptx. Moreover, Ptx-SA significantly attenuates the expression of p-Akt and increases the expression of cleaved PARP and Caspase-3 compared to the equivalent dose of free...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research