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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\u2010 and 7.91\u2010fold 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.<\/jats:p>","DOI":"10.1002\/adhm.201801123","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T12:41:43Z","timestamp":1543408903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["Protein Corona Liposomes Achieve Efficient Oral Insulin Delivery by Overcoming Mucus and Epithelial Barriers"],"prefix":"10.1002","volume":"8","author":[{"given":"Aohua","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Pharmaceutics Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"School of Pharmacy University of Chinese Academy of Sciences  Beijing 100049 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