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

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.