title: Liposomes containing cholesterol analogues of botanical origin as drug delivery systems to enhance the oral absorption of insulin.
abstract: In fear of animal-associated diseases, there is a trend in searching for non-animal derived substitutes for existing excipients in the pharmaceutical industries. This paper aimed to screen cholesterol analogues as membrane stabilizers of liposomes from botanical sterols, including β-sitosterol, stigmasterol, ergosterol and lanosterol. Liposomes containing four kinds of sterols were prepared and evaluated in vitro and in vivo as oral delivery system of insulin. Liposomes containing β-sitosterol (Si-Lip), stigmasterol (St-Lip) and lanosterol (La-Lip) was found not to protect insulin against degradation. Only 10% of the initial insulin in liposomes was preserved after a 30 min exposure to simulated gastric fluids. However, the protective ability of liposomes containing ergosterol (Er-Lip) was similar to that of liposomes containing sodium glycocholate (Sgc-Lip) and superior to that of liposomes containing cholesterol (Ch-Lip). In addition, the blood glucose level can decrease to about 50% of initial level after oral Er-Lip which was significantly superior to the in vivo performance of Si-Lip and Ch-Lip and similar to Sgc-Lip. Er-Lips of ergosterol/phospholipids ratios of 1:4 or 1:6 exerts more pronounced protective ability of insulin in simulated gastrointestinal fluids and hypoglycemic effects in rats than other formulations. Furthermore, Er-Lips exerted low toxicity to Caco-2 cells through a cell viability study. Meahwhile, insulin permeability was significantly increased across Caco-2 monolayers by encapsulating in Er-Lip. It was concluded that ergosterol could be used as a substitute for cholesterol and bile salt derivatives in liposomes to enhance oral bioavailability of insulin.
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai 201203, PR China; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Cui
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai 201203, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Oral Formulation Development, Novo Nordisk A/S, DK-2760 Maalov, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Hovgaard
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai 201203, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: chendawei@syphu.edu.cn.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai 201203, PR China. Electronic address: qijianping@fudan.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D001786:Blood Glucose / Q000032:analysis; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives; D004875:Ergosterol / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008081:Liposomes; D010316:Particle Size; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008081:Liposomes; D002784:Cholesterol; D004875:Ergosterol
keywords: Botanic sterols; Ergosterol; Hypoglycemic; Insulin; Liposome; Oral