Abruzzo Angela, Armenise Nicola, Bigucci Federica, Cerchiara Teresa, Gösser Mireia Broch, Samorì Chiara, Galletti Paola, Tagliavini Emilio, Brown David M, Johnston Helinor J, Fernandes Teresa F, Luppi Barbara
Department of Pharmacy and Biotechnology, Via San Donato 19/2, University of Bologna, 40127 Bologna, Italy.
Department of Chemistry "G. Ciamician", University of Bologna, CIRI EA (Interdepartmental Center of Industrial Research Energy and Environment), Via Selmi 2, 40126 Bologna, Italy.
Int J Pharm. 2017 May 30;524(1-2):9-15. doi: 10.1016/j.ijpharm.2017.03.056. Epub 2017 Mar 27.
One of the most widely used approaches for improving drug permeation across the stratum corneum barrier of the skin is the use of chemical penetration enhancers, such as surfactants. In this study, two anionic surfactants, named C12-OPK and C18-OPK, were synthesized via condensation of itaconic acid and fatty amines, with C12 and C18 alkyl chains, respectively. Assessment of impacts on HaCaT keratinocyte cell viability was used as indicator of their potential to cause skin irritation 24h post exposure (Alamar Blue assay). The LC values of C12-OPK and C18-OPK (144 and 85mg/L, respectively) were lower than LC values of the most used commercial surfactants (e.g. SDS). The effect of different surfactant concentrations (up to ten times the critical micellar concentration, CMC) on hydrocortisone (HC) solubility and permeation through porcine skin was also evaluated. Results showed that drug solubility increased linearly with increasing concentrations of both surfactants, as a consequence of the association between drug and micelles. In vitro permeation results showed that the permeability coefficient increased at surfactant concentrations lower than the CMC. In particular, a higher enhancement effect on drug permeation was obtained with C18-OPK, due to its hydrophobic properties that ensured a more effective HC permeation in comparison to C12-OPK.
提高药物透过皮肤角质层屏障的最广泛使用的方法之一是使用化学渗透促进剂，如表面活性剂。在本研究中，通过衣康酸与脂肪胺缩合分别合成了两种阴离子表面活性剂，命名为C12 - OPK和C18 - OPK，其烷基链分别为C12和C18。通过评估对HaCaT角质形成细胞活力的影响来作为其在暴露24小时后引起皮肤刺激可能性的指标（alamar蓝检测法）。C12 - OPK和C18 - OPK的LC值（分别为144和85mg/L）低于最常用商业表面活性剂（如SDS）的LC值。还评估了不同表面活性剂浓度（高达临界胶束浓度（CMC）的十倍）对氢化可的松（HC）在猪皮中的溶解度和渗透的影响。结果表明，由于药物与胶束之间的缔合，药物溶解度随两种表面活性剂浓度的增加呈线性增加。体外渗透结果表明，在表面活性剂浓度低于CMC时渗透系数增加。特别是，C18 - OPK对药物渗透具有更高的增强作用，这是由于其疏水特性确保了与C12 - OPK相比更有效的HC渗透。
