Enhanced Oral Absorption of Icaritin by Using Mixed Polymeric Micelles Prepared with a Creative Acid-Base Shift Method

Molecules

Xiaoming Chen¹  Kun Meng¹  Xiaoping Ma¹  Hua Yao¹  Haiyan Yin¹  Quntao Wang¹  Mingji Jin¹  Xin Lu¹  Qipeng Yuan²  Cheng Tang² 

[1] Beijing Shenogen Pharmaceutical Co., Ltd., Beijing 102206, China;College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China;

关键词: acid-base shift method;    icaritin;    polymeric micelles;    oral absorption;    transmembrane transport;   

DOI  :  10.3390/molecules26113450

来源: DOAJ

【 摘 要 】

The purpose of this study was to develop mixed polymeric micelles with high drug loading capacity to improve the oral bioavailability of icaritin with Soluplus^® and Poloxamer 407 using a creative acid-base shift (ABS) method, which exhibits the advantages of exclusion of organic solvents, high drug loading and ease of scaling-up. The feasibility of the ABS method was successfully demonstrated by studies of icaritin-loaded polymeric micelles (IPMs). The prepared IPMs were characterized to have a spherical shape with a size of 72.74 ± 0.51 nm, and 13.18% drug loading content. In vitro release tests confirmed the faster release of icaritin from IPMs compared to an oil suspension. Furthermore, bioavailability of icaritin in IPMs in beagle dogs displayed a 14.9-fold increase when compared with the oil suspension. Transcellular transport studies of IPMs across Caco-2 cell monolayers confirmed that the IPMs were endocytosed in their intact forms through macropinocytosis, clathrin-, and caveolae-mediated pathways. In conclusion, the results suggested that the mixed micelles of Soluplus^® and Poloxamer 407 could be a feasible drug delivery system to enhance oral bioavailability of icaritin, and the ABS method might be a promising technology for the preparation of polymeric micelles to encapsulate poorly water-soluble weakly acidic and alkaline drugs.

【 授权许可】

Unknown