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Effect of poly(ethylene glycol) on insulin stability and cutaneous cell proliferation in vitro following cytoplasmic delivery of insulin-loaded nanoparticulate carriers – a potential topical wound management approach

Abdelkader, Dalia H., Osman, Mohamed A., El-Gizawy, Sanaa A., Hawthorne, Susan, Faheem, Ahmed M. and McCarron, Paul A. (2018) Effect of poly(ethylene glycol) on insulin stability and cutaneous cell proliferation in vitro following cytoplasmic delivery of insulin-loaded nanoparticulate carriers – a potential topical wound management approach. European Journal of Pharmaceutical Sciences, 114 . pp. 372-384. [Journal article]

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DOI: 10.1016/j.ejps.2017.12.018

Abstract

We describe the development of a nanoparticulate system, with variation of poly(ethylene glycol) (PEG) content, capable of releasing therapeutic levels of bioactive insulin for extended periods of time. Recombinant human insulin was encapsulated in poly(D,L-lactide-co-glycolide) nanoparticles, manufactured with variation in poly(ethylene glycol) content, and shown to be stable for 6 days using SDS-PAGE, western blot and MALDI MS. To determine if insulin released from this sustained release matrix could stimulate migration of cell types normally active in dermal repair, a model wound was simulated by scratching confluent cultures of human keratinocytes (HaCaT) and fibroblasts (Hs27). Although free insulin was shown to have proliferative effect, closure of in vitro scratch fissures was significantly faster following administration of nano-encapsulated insulin. This effect was more pronounced in HaCaT cells when compared to Hs27 cells. Variation in PEG content had the greatest effect on NP size, with a lesser influence on scratch closure times. Our work supports a particulate uptake mechanism that provides for intracellular insulin delivery, leading to enhanced cell proliferation. When placed into an appropriate topical delivery vehicle, such as a hydrogel, the extended and sustained topical administration of active insulin delivered from a nanoparticulate vehicle shows promise in promoting tissue healing.

Item Type:Journal article
Keywords:Sustained topical deliveryInsulin-loaded PLGA NPsPoly(ethylene glycol)Wound scratch closureKeratinocyteFibroblasts
Faculties and Schools: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
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
ID Code:39261
Deposited By: Professor Paul McCarron
Deposited On:11 Jan 2018 11:21
Last Modified:11 Jan 2018 11:21

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