title: Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: the effect of cholate type, particle size and administered dose.
abstract: Oral delivery of protein or polypeptide drugs remains a challenge due to gastric and enzymatic degradation as well as poor permeation across the intestinal epithelia. In this study, liposomes containing bile salts were developed as a new oral insulin delivery system. The primary goal was to investigate the effect of cholate type, particle size and dosage of the liposomes on the hypoglycemic activity and oral bioavailability. Liposomes containing sodium glycocholate (SGC), sodium taurocholate (STC) or sodium deoxycholate (SDC) were prepared by a reversed-phase evaporation method. After oral administration, all liposomes elicited a certain degree of hypoglycemic effect in parallel with an increase in blood insulin level. The highest oral bioavailability of approximately 8.5% and 11.0% could be observed with subcutaneous insulin as reference for SGC-liposomes in non-diabetic and diabetic rats, respectively. Insulin-loaded liposomes showed slower and sustained action over a period of over 20 h with peak time around 8-12h. SGC-liposomes showed higher oral bioavailability than liposomes containing STC or SDC and conventional liposomes. The hypoglycemic effect was size-dependent with the highest at 150 nm or 400 nm and was proportionally correlated to the administered dose. The results supported the hypothesis of insulin absorption as intact liposomes.
authors.affiliation: Key Laboratory of Smart Drug Delivery, School of Pharmacy, Fudan University, Shanghai, PR China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Niu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Lars
authors.initials: L
authors.lastname: Hovgaard
authors.forename: Peipei
authors.initials: P
authors.lastname: Guan
authors.forename: Yanan
authors.initials: Y
authors.lastname: Tan
authors.forename: Ruyue
authors.initials: R
authors.lastname: Lian
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006000:Glycocholic Acid / Q000008:administration & dosage / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D008081:Liposomes; D003840:Deoxycholic Acid; D013656:Taurocholic Acid; D006000:Glycocholic Acid