Shah Sayyed I, Khutoryanskiy Vitaliy V, Williams Adrian C
Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK.
Pharmaceutics. 2021 Mar 18;13(3):403. doi: 10.3390/pharmaceutics13030403.
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).
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 H NMR and FT-IR, analysed by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), molecular weights and reactivity ratios determined, and repellent loading assessed.
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.
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.
我们开发了一种新型聚合物驱虫共轭物，用于延长挥发性驱虫剂对薄荷烷-3,8-二醇（PMD）的释放并减少其皮肤渗透。
PMD通过酯键与丙烯酰氯共轭形成丙烯酰-PMD，随后将其与丙烯酸以不同摩尔比共聚。通过核磁共振氢谱（H NMR）和傅里叶变换红外光谱（FT-IR）对共聚物结构进行表征，通过热重分析（TGA）、差示扫描量热法（DSC）进行分析，测定分子量和反应比，并评估驱虫剂负载量。
使用猪肝酯酶，约45%的驱虫剂在五天内释放。使用切除的完整猪耳皮肤对共聚物和游离驱虫剂进行的渗透和透皮研究表明，与PMD相比，共聚物未检测到透过皮肤的渗透。此外，胶带剥离显示超过90%的共聚物留在皮肤外表面，而游离PMD存在于所有皮肤层中。涡虫毒性荧光测定表明，局部应用时该共聚物不太可能是一种显著的刺激物。
本研究证明了共聚物方法用于开发缓释驱虫剂的可行性，同时减少小分子活性成分的皮肤吸收和透皮渗透，以尽量减少任何不良影响。
