Ding Ruihuan, Zhao Zhenyu, He Jibiao, Tao Yuping, Zhang Houqian, Yuan Ranran, Sun Kaoxiang, Shi Yanan
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 261400, China.
School of Life Science, Yantai University, Yantai 261400, China.
Nanomaterials (Basel). 2023 Jan 29;13(3):540. doi: 10.3390/nano13030540.
The development of oral drug delivery systems is challenging, and issues related to the mucus layer and low intestinal epithelial permeability have not yet been surmounted. The purpose of this study was to develop a promising formulation that is more adapted to in vivo absorption and to facilitate the administration of oral liraglutide. Cationic liposomes (CLs) linked to AT-1002 were prepared using a double-emulsion method, and BSA was adsorbed on the surface of the AT-CLs, resulting in protein corona cationic liposomes with AT-1002 (Pc-AT-CLs). The preparation method was determined by investigating various process parameters. The particle size, potential, and encapsulation efficiency (EE%) of the Pc-AT-CLs were 202.9 ± 12.4 nm, 1.76 ± 4.87 mV, and 84.63 ± 5.05%, respectively. The transmission electron microscopy (TEM) imaging revealed a nearly spherical structure of the Pc-AT-CLs, with a recognizable coating. The circular dichroism experiments confirmed that the complex preparation process did not affect the secondary structure of liraglutide. With the addition of BSA and AT-1002, the mucosal accumulation of the Pc-AT-CLs was nearly two times lower than that of the AT-CLs, and the degree of enteric metaplasia was 1.35 times higher than that of the PcCLs. The duration of the intestinal absorption of the Pc-AT-CLs was longer, offering remarkable biological safety.
口服给药系统的开发具有挑战性，与黏液层和低肠上皮渗透性相关的问题尚未得到解决。本研究的目的是开发一种更适合体内吸收并便于口服利拉鲁肽给药的有前景的制剂。采用复乳法制备与AT - 1002连接的阳离子脂质体（CLs），并将牛血清白蛋白（BSA）吸附在AT - CLs表面，得到具有AT - 1002的蛋白冠阳离子脂质体（Pc - AT - CLs）。通过研究各种工艺参数确定制备方法。Pc - AT - CLs的粒径、电位和包封率（EE%）分别为202.9±12.4 nm、1.76±4.87 mV和84.63±5.05%。透射电子显微镜（TEM）成像显示Pc - AT - CLs具有近乎球形的结构，有可识别的包衣。圆二色性实验证实复合制备过程不影响利拉鲁肽的二级结构。加入BSA和AT - 1002后，Pc - AT - CLs的黏膜蓄积量比AT - CLs低近两倍，肠化生程度比PcCLs高1.35倍。Pc - AT - CLs的肠道吸收持续时间更长，具有显著的生物安全性。
