Sodium glycocholate liposome encapsulated semaglutide increases oral bioavailability by promoting intestinal absorption

• Published in: International journal of pharmaceutics 2024-11, Vol.665, p.124669, Article 124669
• Main Authors: Li, Yehan, Liu, Fei, Che, Jiajing, Zhang, Yu, Yin, Tian, Gou, Jingxin, Tang, Xing, Wang, Yanjiao, He, Haibing
• Format: Article
• Language: English
• Subjects: liposomes containing bile salts; oral administration; Semaglutide; stability
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124669

[Display omitted] The aim of this study was to prepare sodium glycocholate liposomes (SGC-Lip) encapsulating semaglutide (Sml) to improve oral bioavailability and better exert hypoglycemic effect. In this paper, SGC-Lip was prepared by reverse-phase evaporation method with particle size around 140 nm, potential around -27 mV, rounded morphology and better stability. The hypoglycemic and intestinal uptake effects of SGC-Lip and cholesterol-containing liposomes (CH-Lip) were comparatively investigated in rats, and the oral safety of SGC-Lip was examined by cytotoxicity assay. The results indicate that SGC-Lip can achieve a hypoglycemic effect of 40% of the initial value within 12 hours, and the AAC0-12h is approximately six times that of CH-Lip without sodium glycocholate. The results of the cytotoxicity tests indicate that SGC-Lip has good oral safety. SGC-Lip enhances the absorption of semaglutide in the small intestinal villi via an apical sodium-dependent bile acid transporter (ASBT)-mediated pathway with the highest penetration at the ileal site. In summary, the oral bioavailability of semaglutide can be improved by encapsulating semaglutide in SGC-Lip and utilizing the stabilizing and permeation-promoting effects of SGC on liposomes.