A Novel Polymer Insect Repellent Conjugate for Extended Release and Decreased Skin Permeation of Para-Menthane-3,8-Diol

Abstract

Background: We developed a novel polymer insect repellent conjugate for extended release and decreased skin permeation of the volatile insect repellent p-menthane-3,8-diol (PMD). Methods: PMD was conjugated with acryloyl chloride via an ester bond to form acryloyl–PMD, which was subsequently copolymerised with acrylic acid at varying molar ratios. Copolymer structures were characterised by 1H NMR and FT-IR, analysed by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), molecular weights and reactivity ratios determined, and repellent loading assessed. Results: Using porcine liver esterases, ~45% of the insect repellent was released over five days. Penetration and permeation studies of the copolymer and free repellent using excised, full-thickness porcine ear skin showed no detectable permeation of the copolymer through skin compared to the PMD. Moreover, tape stripping revealed that over 90% of the copolymer remained on the outer surface of the skin, whereas free PMD was within all skin layers. A planarian toxicity fluorescence assay indicated that that the copolymer is unlikely to be a significant irritant when applied topically. Conclusions: this study demonstrates the feasibility of the copolymer approach to develop extended-release insect repellents while reducing skin uptake and transdermal permeation of the small-molecular-weight active ingredient, in order to minimise any adverse effects.

Keywords

• polymer–drug conjugate
• extended release
• skin
• insect repellent
• p-menthane-3,8-diol
• PMD