Padula Cristina, Pescina Silvia, Nicoli Sara, Santi Patrizia
Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy.
Pharmaceutics. 2018 Oct 24;10(4):201. doi: 10.3390/pharmaceutics10040201.
Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics and vaccines. The aim of this work was to gain insight into the mechanism of fatty acids as buccal permeation enhancers, by studying the effect of a series of medium and long chain fatty acids on the permeation of a model high molecular weight and hydrophilic molecule, fluorescein isothiocyanate labelled dextran (FD-4, m.w. 4 kDa) across porcine esophageal epithelium. A parabolic relationship between fatty acid lipophilicity and enhancement was obtained, regardless of the presence and number of double bonds. The relationship, which resembles the well-known relationship between permeability and lipophilicity of transdermal delivery, presents a maximum value in correspondence of C10 (logP 4). This is probably the ideal lipophilicity for the fatty acid to interact with the lipid domains of the mucosa. When the same analysis was performed on skin data, the same trend was observed, although the maximum value was reached for C12 (logP 5), in agreement with the higher lipophilicity of the skin. The results obtained in the present work represent a significant advancement in the understanding of the mechanisms of action of fatty acids as buccal penetration enhancers.
颊黏膜作为包括生物制品和疫苗在内的药物全身给药的潜在途径，近来备受关注。本研究的目的是通过研究一系列中链和长链脂肪酸对一种模型高分子量亲水性分子——异硫氰酸荧光素标记的葡聚糖（FD-4，分子量4 kDa）透过猪食管上皮细胞渗透的影响，深入了解脂肪酸作为颊黏膜渗透促进剂的作用机制。无论双键的存在与否及数量多少，脂肪酸亲脂性与促进作用之间均呈现抛物线关系。这种关系类似于经皮给药中渗透率与亲脂性之间的著名关系，在C10（logP 4）时呈现最大值。这可能是脂肪酸与黏膜脂质域相互作用的理想亲脂性。当对皮肤数据进行同样的分析时，观察到相同的趋势，尽管在C12（logP 5）时达到最大值，这与皮肤较高的亲脂性一致。本研究获得的结果代表了在理解脂肪酸作为颊黏膜渗透促进剂的作用机制方面取得的重大进展。
