title: Pluronic P85/poly(lactic acid) vesicles as novel carrier for oral insulin delivery.
abstract: Poly(lactic acid)-b-Pluronic-b-poly(lactic acid) (PLA-P85-PLA) vesicles were developed as novel carrier for oral insulin delivery. PLA-P85-PLA block copolymer was synthesized by ring opening polymerization of the monomer l-lactide using Pluronic copolymer P85 as the initiator. Insulin-loaded PLA-P85-PLA vesicles were prepared by dialysis method and the mean diameter of insulin-loaded PLA-P85-PLA vesicles was determined to be 178 nm. The cytotoxicity studies using human ovarian cancer cells OVCAR-3 indicate that PLA-P85-PLA block copolymer has good biocompatibility. Both in vitro and in vivo release behavior of insulin loaded in PLA-P85-PLA vesicles were studied. It was observed that insulin was released out gradually from PLA-P85-PLA vesicles and almost all insulin was released out 7.5h later. More importantly, for the oral administration of insulin-loaded PLA-P85-PLA vesicles at insulin doses of 200 IU/kg, the minimum blood glucose concentration was observed in the diabetic mice test after 2.5h, which was 15% of initial glucose level. Furthermore, the blood glucose concentration increased slowly to 31.8% of initial blood glucose concentration after 10.5h and was maintained at this level for at least an additional 14h (32.5% of initial blood glucose concentration at 24.5h). These results proved that PLA-P85-PLA vesicles could be promising polymeric carriers for oral insulin delivery application due to their sustained and enhanced hypoglycemic effect.
authors.affiliation: School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, China. Electronic address: xyxiong@gmail.com.
authors.forename: Xiang Yuan
authors.initials: XY
authors.lastname: Xiong
authors.affiliation: School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Qi Han
authors.initials: QH
authors.lastname: Li
authors.affiliation: School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Yu Ping
authors.initials: YP
authors.lastname: Li
authors.affiliation: School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.affiliation: School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Zi Ling
authors.initials: ZL
authors.lastname: Li
authors.affiliation: School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, China.
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Gong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects; D002850:Chromatography, Gel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011060:Poloxalene / Q000138:chemical synthesis / Q000737:chemistry; D011091:Polyesters; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D007328:Insulin; D011091:Polyesters; D011108:Polymers; D053835:Unilamellar Liposomes; C422648:pluronic block copolymer p85; D019344:Lactic Acid; C033616:poly(lactide); D011060:Poloxalene
keywords: Biocompatible; Insulin; Oral delivery; PLA-P85-PLA block copolymer; Vesicles