title: Improving oral bioavailability and pharmacokinetics of liposomal metformin by glycerolphosphate-chitosan microcomplexation.
abstract: The purpose of this study was to develop a new delivery system capable of improving bioavailability and controlling release of hydrophilic drugs. Metformin-loaded liposomes were prepared and to improve their stability surface was coated with chitosan cross-linked with the biocompatible β-glycerolphosphate. X-ray diffraction, differential scanning calorimetry, as well as rheological analysis were performed to investigate interactions between chitosan and β-glycerolphosphate molecules. The entrapment of liposomes into the chitosan-β-glycerolphosphate network was assessed by scanning electron microscopy and transmission electron microscopy. Swelling and mucoadhesive properties as well as drug release were evaluated in vitro while the drug oral bioavailability was evaluated in vivo on Wistar rats. Results clearly showed that, compared to control, the proposed microcomplexes led to a 2.5-fold increase of metformin T(max) with a 40% augmentation of the AUC/D value.
authors.affiliation: Dept. Scienze della Vita e dell'Ambiente, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy. manconi@unica.it
authors.forename: Maria
authors.initials: M
authors.lastname: Manconi
authors.forename: Amparo
authors.initials: A
authors.lastname: Nácher
authors.forename: Virginia
authors.initials: V
authors.lastname: Merino
authors.forename: Matilde
authors.initials: M
authors.lastname: Merino-Sanjuan
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Manca
authors.forename: Carla
authors.initials: C
authors.lastname: Mura
authors.forename: Simona
authors.initials: S
authors.lastname: Mura
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Fadda
authors.forename: Octavio
authors.initials: O
authors.lastname: Diez-Sales
mesh_terms: D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005753:Gastric Mucosa / Q000378:metabolism; D005994:Glycerophosphates / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008081:Liposomes; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005994:Glycerophosphates; D007004:Hypoglycemic Agents; D008081:Liposomes; D048271:Chitosan; D008687:Metformin