Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization

Drug Delivery

Sihuan Gao¹  Xiaoqin Wang¹  Xiaoling Fu¹  Yanfang Wang¹  Ying Xu²  Qing Hu²  Changxi Yu²  Yanping Su² 

[1] School of Pharmacy, Fujian Medical University, Fuzhou, Chin;School of Pharmacy, Fujian Medical University, Fuzhou, Chin;Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, Chin;

关键词: Koumine;    hydroxypropyl-β-cyclodextrin;    inclusion complexes;    permeability;    bioavailability;   

DOI  :  10.1080/10717544.2021.1998248

来源: Taylor & Francis

【 摘 要 】

Koumine (KME) is an active alkaloid extracted from Gelsemium elegans, and its diverse bioactivities have been studied for decades. However, KME exhibits poor solubility and low oral bioavailability, which hampers its potential therapeutic exploitation. This work aimed to develop optimized inclusion complexes to improve the bioavailability of KME. The KME/hydroxypropyl-β-cyclodextrin (KME/HP-β-CD) inclusion complexes were prepared by the solvent evaporation method and later optimized using the Box-Behnken design. The optimal KME/HP-β-CD was characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, differential scanning calorimetry, and nuclear magnetic resonance spectroscopy. The physicochemical characterization results revealed that the crystalline state of KME was transformed into an amorphous form, forming KME/HP-β-CD inclusion complexes. Compared with KME, the solubility and in vitro release rate of KME/HP-β-CD was significantly enhanced by 52.34- and 1.3-fold, respectively. Further research was performed to investigate the intestinal absorption characteristics and in vivo bioavailability in rats. The optimal KME/HP-β-CD showed enhanced absorptive permeability and relative bioavailability increased more than two-fold compared to that of raw KME. These results indicate that the optimal KME/HP-β-CD can be used as an effective drug carrier to improve the solubility, intestinal absorption, and bioavailability of KME.

【 授权许可】

CC BY