title: Biotinylated liposomes as potential carriers for the oral delivery of insulin.
abstract: This study aimed to explore biotinylated liposomes (BLPs) as novel carriers to enhance the oral delivery of insulin. Biotinylation was achieved by incorporating biotin-conjugated phospholipids into the liposome membranes. A significant hypoglycemic effect and enhanced absorption were observed after treating diabetic rats with the BLPs with a relative bioavailability of 12.09% and 8.23%, based on the measurement of the pharmacologic effect and the blood insulin level, respectively; this achieved bioavailability was approximately double that of conventional liposomes. The significance of the biotinylation was confirmed by the facilitated absorption of the BLPs through receptor-mediated endocytosis, as well as by the improved physical stability of the liposomes. Increased cellular uptake and quick gastrointestinal transport further verified the ability of the BLPs to enhance absorption. These results provide a proof of concept that BLPs can be used as potential carriers for the oral delivery of insulin.
  
  
  BACKGROUND
  Diabetes remains a major source of mortality in the Western world, and advances in its management are expected to have substantial socioeconomic impact. In this paper, biotinylated liposomes were utilized as carriers of insulin for local delivery, demonstrating the feasibility of this approach in a rat model.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, PR China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, PR China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, PR China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, PR China. Electronic address: wuwei@shmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007328:Insulin; D008081:Liposomes
keywords: 1,2-distearoyl-sn-glycero-3-phosphatidyl ethanolamine; BLPs; Biotin; CD; CLPs; CLSM; DSPE; EE; FITC; GI; Insulin; Liposomes; MFI; Oral delivery; P(app); PA; Receptor-mediated endocytosis; SGF; SIF; SPC; T(t); TEM; apparent permeability; biotinylated liposomes; circular dichroism; confocal laser scanning microscope; conventional liposomes; entrapment efficiency; fluorescent isothiocyanate; gastrointestinal; mean fluorescence intensity; pharmacological bioavailability; phase transition temperature; s.c; simulated gastric fluid; simulated intestinal fluid; soybean phosphatidylcholine; subcutaneous; transmission electron microscopy