Enhanced Oral Absorption of Icaritin by Using Mixed Polymeric Micelles Prepared with a Creative Acid-Base Shift Method |
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| Authors: | Cheng Tang Xiaoming Chen Hua Yao Haiyan Yin Xiaoping Ma Mingji Jin Xin Lu Quntao Wang Kun Meng Qipeng Yuan |
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| Institution: | 1.College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China;2.Beijing Shenogen Pharmaceutical Co., Ltd., Beijing 102206, China; (X.C.); (H.Y.); (H.Y.); (X.M.); (M.J.); (X.L.); (Q.W.); (K.M.) |
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| Abstract: | 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. |
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| Keywords: | acid-base shift method icaritin polymeric micelles oral absorption transmembrane transport |
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