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Poly(N-isopropyl acrylamide)–poly(ethylene glycol)–poly(N-isopropyl acrylamide) as a thermoreversible gelator for topical administration

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Abstract

Poly(N-isopropyl acrylamide)-block-poly(ethylene glycol)-block-poly(N-isopropyl acrylamide) is known to exhibit a thermally-induced solution-to-gel transition in water, which may be exploited for biomedical applications. This “thermoreversible gelator” has great potential for application in topical administration to the surfaces of the body such as the skin, eye, and vagina, but this has not yet been evaluated. This study evaluates PNIPAM98–PEG122–PNIPAM98 as a thermoreversible gelator for vaginal administration, for the first time evaluating the effect of polymer concentration on gelation, studying rheological parameters relevant to topicals, measuring dissolution rates, stability and the phenomenon of mucoadhesion. Two drugs relevant to vaginal administration, progesterone and tenofovir disoproxil fumarate are investigated for use in the thermoreversible gelators, studying both hydrophobic and hydrophilic drug solubilisation and release. Throughout the study, comparison is made with poloxamer 407, the most commonly studied thermoreversible gelator. PNIPAM98–PEG122–PNIPAM98 exhibits several advantages for topical administration, having low viscosity at room temperature to allow easy application, then exhibiting a gelation just below body temperature to form a viscous gel which is resistant to dissolution and relatively mucoadhesive. Drug release is highly dependent on temperature, with elevation to body temperature resulting in a dramatic retardation of progesterone release, which may be used in future medicines to provide sustained delivery of hydrophobic xenobiotics.

Graphical abstract: Poly(N-isopropyl acrylamide)–poly(ethylene glycol)–poly(N-isopropyl acrylamide) as a thermoreversible gelator for topical administration

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Supplementary files

Article information


Submitted
05 Mar 2020
Accepted
06 May 2020
First published
06 May 2020

This article is Open Access

Mater. Adv., 2020, Advance Article
Article type
Paper

Poly(N-isopropyl acrylamide)–poly(ethylene glycol)–poly(N-isopropyl acrylamide) as a thermoreversible gelator for topical administration

P. Haddow, W. J. McAuley, S. B. Kirton and M. T. Cook, Mater. Adv., 2020, Advance Article , DOI: 10.1039/D0MA00080A

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