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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

Haggag, Yusuf, Faheem, Ahmed, Tambuwala, Murtaza, Osman, Mohamed, El-Gizawy, Sanna, O'Hagan, Barry, Irwin, Nigel and McCarron, Paul (2017) 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. Pharmaceutical Development and Technology, N/A . [Journal article]

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URL: http://dx.doi.org/10.1080/10837450.2017.1295066

DOI: 10.1080/10837450.2017.1295066

Abstract

Context Size, encapsulation efficiency and stability affect the sustained release from nanoparticles containing protein-type drugs.Objectives Insulin was used to evaluate effects of formulation parameters on minimising diameter, maximising encapsulation efficiency and preserving blood glucose control following intraperitoneal (IP) administration. Methods Homogenisation or sonication was used to incorporate insulin into poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with increasing PEG content. Effects of polymer type, insulin/polymer loading ratio and stabiliser 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, whilst absence of internal stabiliser improved encapsulation and minimised burst release kinetics. Homogenisation 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 hours in diabetic mice following a single bolus, with no evidence of hypoglycaemia.Conclusions Insulin-loaded NP prepared from 10% PEG-PLGA possessed therapeutically useful encapsulation and release kinetics when delivered by the IP route.

Item Type:Journal article
Keywords:insulin, nanoparticles, diblock copolymers, encapsulation efficiency, intraperitoneal bioactivity
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute > Genomic Medicine
Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
Biomedical Sciences Research Institute > Diabetes
ID Code:37074
Deposited By: Professor Paul McCarron
Deposited On:06 Mar 2017 09:11
Last Modified:18 Sep 2017 11:34

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