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

• Main Authors: Sayyed I. Shah (Author), Vitaliy V. Khutoryanskiy (Author), Adrian C. Williams (Author)
• Format: Book
• Published: MDPI AG, 2021-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics13030403; 1999-4923
• Keywords: polymer-drug conjugate; extended release; skin; insect repellent; p-menthane-3,8-diol; PMD; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 13, Iss 3, p 403 (2021)

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.