Water-Soluble Combretastatin A4 Phosphate Orally Delivered via Composite Nanoparticles With Improved Inhibition Effect Toward S180 Tumors

作者：Shen, Yurun; Wu, Liping; Qiu, Liyan^*

来源：Journal of Pharmaceutical Sciences, 2017, 106(10): 3076-3083.

DOI：10.1016/j.xphs.2017.05.031

• combretastatin A4 phosphate
• nanoparticles
• oral absorption
• bioavailability
• cancer therapy

Combretastatin A4 phosphate (CA4P) is a novel vascular disrupting agent for cancer therapy. However, frequent dosing and negative patient compliance have been encountered over CA4P by injection administration due to its quite short-term action and acute side effects. Therefore, it is significant to develop an oral formulation of CA4P. We established a novel method to prepare CA4P-loaded nanoparticles (CA4P-NPs) for oral administration by combining methoxy poly(ethylene glycol)-b-polylactide (PELA) and poly(D,L-lactic-co-glycolic acid) (PLGA) polymers. Transport study in vitro was evaluated on Madin-Darby canine kidney cell models, and antitumor effect evaluation in vivo was performed on S180 subcutaneous xenotransplanted tumor models in mice. The highest entrapment efficiency of CA4P-NPs was achieved when the weight ratio of PELA to PLGA was optimized to 1:1. The apparent permeability coefficient of CA4P-NPs was found to be 2.08-fold higher than that of free CA4P in transport study. CA4P-NPs reached an absolute bioavailability of 77.6% with the tumor inhibition ratio of 41.2% that was significantly superior to free CA4P. These results suggest a promising application of this composite nanoparticle for the oral delivery of water-soluble drugs.

• 出版日期2017-10
• 单位浙江大学