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Published on: July 30, 2020
Roxadustat-loaded pH-sensitive Anionic Liposomes Ameliorating Experimental Colitis in Mice: Formulation, Cellular
Guiping Kong1, Yucan Zheng1, Yan Lu1
1Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, China.
Introduction:
Roxadustat, an inhibitor of hypoxia-inducible factor prolyl hydroxylase, has therapeutic potential for colitis but is limited clinically by poor water solubility and rapid gastrointestinal absorption. This study aimed to develop a pH-responsive, intestinal-targeted nanocarrier to enhance its oral bioavailability and anti-colitis efficacy.
Methods:
Roxadustat-loaded liposomes (ROX-LP) were prepared via thin-film hydration with DSPG-PEG2000, cholesterol, and sodium cholate, then coated with Kollicoat MAE 100 P to form ROX-MAE@LP. The formulation was evaluated for physicochemical properties, in vitro release, cellular uptake, pharmacokinetics, and in vivo therapeutic efficacy.
Results:
ROX-MAE@LP showed excellent encapsulation and uniform spherical morphology, with pH-dependent release (markedly increased at pH 6.8 and 7.4). Enhanced cellular uptake was observed in Caco-2 cells under intestinal pH-mimicking conditions. In rats, the oral bioavailability of ROX-LP (150.32±9.22%) and ROX-MAE@LP (255.36±12.82%) was improved compared with roxadustat suspension, and ROX-MAE@LP had a prolonged mean residence time (14.66±1.97 h). In a murine dextran sulfate sodium-induced colitis model, ROX-MAE@LP alleviated inflammation, downregulated pro-inflammatory cytokines, and promoted mucosal repair, outperforming ROX-LP and free roxadustat.
Discussion:
The pH-responsive coating and intestinal-targeted property of ROX-MAE@LP effectively address the poor solubility and rapid absorption of roxadustat, enhancing local intestinal concentration and therapeutic effect in colitis, showing high potential for oral inflammatory bowel disease therapy.
Conclusion:
ROX-MAE@LP is an effective intestine-targeted delivery system that improves roxadustat's solubility, bioavailability and therapeutic outcomes in inflammatory bowel disease, while offering additional options for the development of novel roxadustat-based preparations and pHresponsive nanocarriers.
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