title: Effect of poly(ethylene glycol) content and formulation parameters on particulate properties and intraperitoneal delivery of insulin from PLGA nanoparticles prepared using the double-emulsion evaporation procedure.
abstract: BACKGROUND
  Size, encapsulation efficiency and stability affect the sustained release from nanoparticles containing protein-type drugs.
  
  
  OBJECTIVE
  Insulin was used to evaluate effects of formulation parameters on minimizing diameter, maximizing encapsulation efficiency and preserving blood glucose control following intraperitoneal (IP) administration.
  
  
  METHODS
  Homogenization or sonication was used to incorporate insulin into poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with increasing poly(ethylene glycol) (PEG) content. Effects of polymer type, insulin/polymer loading ratio and stabilizer in the internal aqueous phase on physicochemical characteristics of NP, in vitro release and stability of encapsulated insulin were investigated. Entrapment efficiency and release were assessed by radioimmunoassay and bicinconnic acid protein assay, and stability was evaluated using SDS-PAGE. Bioactivity of insulin was assessed in streptozotocin-induced, insulin-deficient Type I diabetic mice.
  
  
  RESULTS
  Increasing polymeric PEG increased encapsulation efficiency, while the absence of internal stabilizer improved encapsulation and minimized burst release kinetics. Homogenization was shown to be superior to sonication, with NP fabricated from 10% PEG-PLGA having higher insulin encapsulation, lower burst release and better stability. Insulin-loaded NP maintained normoglycaemia for 24 h in diabetic mice following a single bolus, with no evidence of hypoglycemia.
  
  
  CONCLUSIONS
  Insulin-loaded NP prepared from 10% PEG-PLGA possessed therapeutically useful encapsulation and release kinetics when delivered by the IP route.
authors.affiliation: a School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes , Ulster University , Coleraine, Co. Londonderry , UK.|b Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Tanta , Tanta , Egypt.
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Haggag
authors.affiliation: c Department of Pharmacy, Health and Well-being , University of Sunderland , Sunderland , UK.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Faheem
authors.affiliation: a School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes , Ulster University , Coleraine, Co. Londonderry , UK.
authors.forename: Murtaza M
authors.identifier: http://orcid.org/0000-0001-8499-9891
authors.initials: MM
authors.lastname: Tambuwala
authors.affiliation: b Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Tanta , Tanta , Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Osman
authors.affiliation: b Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Tanta , Tanta , Egypt.
authors.forename: Sanaa A
authors.initials: SA
authors.lastname: El-Gizawy
authors.affiliation: d School of Biomedical Sciences , Ulster University , Cromore Road , Coleraine, Co. Londonderry , UK.
authors.forename: Barry
authors.initials: B
authors.lastname: O'Hagan
authors.affiliation: a School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes , Ulster University , Coleraine, Co. Londonderry , UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Irwin
authors.affiliation: a School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes , Ulster University , Coleraine, Co. Londonderry , UK.
authors.forename: Paul A
authors.identifier: http://orcid.org/0000-0002-2292-9887
authors.initials: PA
authors.lastname: McCarron
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004655:Emulsions / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D007004:Hypoglycemic Agents; D007328:Insulin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols
keywords: Insulin; diblock copolymers; encapsulation efficiency; intraperitoneal bioactivity; nanoparticles