Center for Pharmaceutics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
School of Pharmacy, University of Chinese Academy of Sciences, Beijing, 100049, China.
Adv Healthc Mater. 2019 Jun;8(12):e1801123. doi: 10.1002/adhm.201801123. Epub 2018 Nov 28.
Oral delivery of peptide/protein drugs has attracted worldwide attention due to its good patient compliance and convenience of administration. Orally administered nanocarriers always encounter the rigorous defenses of the gastrointestinal tract, which mainly consist of mucus and epithelium barriers. However, diametrically opposite surface properties of nanocarriers are required for good mucus penetration and high epithelial uptake. Here, bovine serum albumin (BSA) is adsorbed to cationic liposomes (CLs) to form protein corona liposomes (PcCLs). The aim of using PcCLs is to conquer the mucus and epithelium barriers, eventually improving the oral bioavailability of insulin. Investigations using in vitro and in vivo experiments show that the uptake amounts and transepithelial permeability of PcCLs are 3.24- and 7.91-fold higher than that of free insulin, respectively. Further study of the behavior of PcCLs implies that BSA corona can be shed from PcCLs as they cross the mucus layer, which results in the exposure of CLs to improve the transepithelial transport. Intrajejunal administration of PcCLs in type I diabetic rats produces a remarkable hypoglycemic effect and increases the oral bioavailability up to 11.9%. All of these results imply that PcCLs may provide a new insight into the method for oral insulin delivery by overcoming the multiple barriers.
口服递药系统由于其良好的顺应性和给药方便，引起了全世界的关注。口服给予的纳米载体总是会遇到胃肠道的严格防御，主要由粘液和上皮屏障组成。然而，良好的粘液穿透和高上皮摄取需要纳米载体具有截然相反的表面性质。在这里，牛血清白蛋白（BSA）被吸附到阳离子脂质体（CL）上形成蛋白冠脂质体（PcCL）。使用 PcCL 的目的是克服粘液和上皮屏障，最终提高胰岛素的口服生物利用度。使用体外和体内实验的研究表明，PcCL 的摄取量和跨上皮通透性分别比游离胰岛素高 3.24 倍和 7.91 倍。对 PcCL 行为的进一步研究表明，当 PcCL 穿过粘液层时，BSA 冠可以从 PcCL 上脱落，从而使 CL 暴露出来，以改善跨上皮转运。PcCL 在 I 型糖尿病大鼠的空肠内给药产生显著的降血糖作用，并将口服生物利用度提高至 11.9%。所有这些结果表明，PcCL 可能通过克服多种屏障为口服胰岛素递送提供了一种新的方法。
