title: Preparation and in vivo evaluation of insulin-loaded biodegradable nanoparticles prepared from diblock copolymers of PLGA and PEG.
abstract: The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (DL-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200-400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3h to 6 days in type I diabetic mice.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes, Ulster University, Cromore Road, Coleraine, Co. Londonderry BT52 1SA, UK; Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Tanta, Tanta, Egypt.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Haggag
authors.affiliation: School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, Co.Londonderry BT52 1SA, UK.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Abdel-Wahab
authors.affiliation: School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, Co.Londonderry BT52 1SA, UK; School of Sport, Health and Bioscience, University of East London, Stratford E15 4lZ, UK.
authors.forename: Opeolu
authors.initials: O
authors.lastname: Ojo
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Tanta, Tanta, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Osman
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Tanta, Tanta, Egypt.
authors.forename: Sanaa
authors.initials: S
authors.lastname: El-Gizawy
authors.affiliation: Institute of Cancer Therapeutics, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Tanani
authors.affiliation: University of Sunderland, Department of Pharmacy, Health and Well-being, Sunderland Pharmacy School, Sunderland SR1 3SD, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Faheem
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes, Ulster University, Cromore Road, Coleraine, Co. Londonderry BT52 1SA, UK. Electronic address: p.mccarron@ulster.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: McCarron
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D007004:Hypoglycemic Agents; D007328:Insulin; D011091:Polyesters; D012997:Solvents; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols
keywords: Controlled delivery; Diabetes; Insulin; Nanoparticles; PEG-PLGA; Stability