Programa de Pós-Graduação em Farmácia, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
AAPS PharmSciTech. 2020 Oct 20;21(8):289. doi: 10.1208/s12249-020-01827-5.
The oral administration of isoniazid (INH) may lead to discontinuation of tuberculosis treatment due to drug-related hepatotoxicity events, and thus, the transbuccal delivery of this drug was investigated, for the first time, as an alternative administration route. Ex vivo permeability assays were performed in Franz-type diffusion chambers, applying INH alone and in combination with sodium dodecyl sulfate (SDS) and sodium taurocholate (ST). After confirming the formation of micelle structures by dynamic light scattering analysis, UV-visible spectroscopy and zeta potential analyses were used to investigate drug-micelle interactions. In zeta potential analyses, no electrostatical interactions were identified for both surfactants in saliva buffer pH 6.8. Spectrophotometric analyses, in turn, indicated chemical interactions between INH and SDS in both pH values (2.0 and 6.8) whereas no interaction between the drug and ST was observed. Despite the interaction between SDS and drug, this surfactant increased the buccal transport rate of INH by approximately 11 times when compared with the control. In contrast, ST did not increase the drug permeability. The INH retention in SDS-treated mucosa was significantly higher when compared with the control and an effect on intercellular lipids was suggested. In vivo studies are needed to confirm the high INH absorption found here. Grapical abstract.
异烟肼（INH）的口服给药可能会由于与药物相关的肝毒性事件而导致结核病治疗的中断，因此首次研究了经颊给药作为替代给药途径。在 Franz 型扩散室中进行了体外渗透测定，单独应用 INH 以及与十二烷基硫酸钠（SDS）和牛磺胆酸钠（ST）联合应用。通过动态光散射分析、紫外可见光谱和ζ电位分析确认形成胶束结构后，用于研究药物-胶束相互作用。在ζ电位分析中，两种表面活性剂在唾液缓冲液 pH 6.8 中均未发现静电相互作用。分光光度分析表明，在两种 pH 值（2.0 和 6.8）下 INH 与 SDS 之间均存在化学相互作用，而药物与 ST 之间未观察到相互作用。尽管 SDS 与药物之间存在相互作用，但与对照相比，该表面活性剂使 INH 的颊侧转运速率增加了约 11 倍。相反，ST 并未增加药物的通透性。与对照相比，SDS 处理的粘膜中 INH 的保留率显著更高，提示对细胞间脂质有影响。需要进行体内研究来证实此处发现的高 INH 吸收。
