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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, D H, Osman, M. A., El-Gizawy, S. A., Hawthorne, S. J., Faheem, Ahmed and McCarron, P. 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. ISSN 0928-0987

Item Type: Article

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 6days 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.

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More Information

Depositing User: Barry Hall

Identifiers

Item ID: 8645
Identification Number: https://doi.org/10.1016/j.ejps.2017.12.018
ISSN: 0928-0987
URI: http://sure.sunderland.ac.uk/id/eprint/8645
Official URL: http://www.sciencedirect.com/science/article/pii/S...

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Catalogue record

Date Deposited: 15 Jan 2018 11:50
Last Modified: 30 Sep 2020 11:16

Contributors

Author: D H Abdelkader
Author: M. A. Osman
Author: S. A. El-Gizawy
Author: S. J. Hawthorne
Author: Ahmed Faheem
Author: P. A. McCarron

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences

Subjects

Sciences > Biomedical Sciences
Sciences > Pharmacy and Pharmacology

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