The relevance of nanotechnology, hepato-protective agents in reducing the toxicity and augmenting the bioavailability of isotretinoin

Acne Vulgaris is one of the most common chronic inflammatory skin disorders that affect majority of teen-agers worldwide. Isotretinoin (ITT) is the drug of choice in the management of acne, but, it suffers from serious side-effects including hepatotoxicity, and some psychological disturbances following its oral intake. The objective of this study was to develop and optimize ITT loaded nanoemulsions (ITT-SNEDDS) and to incorporate resveratrol (RSV)in optimum formulation to decrease ITT side effects The ITT solubility was first tested in various essential oils, surfactants, and co-surfactants to select the essential nanoemulsion ingredients. Mixture design was applied to study the effect of independent variables and their interactions on the selected dependent responses. The developed ITT-SNEDDS were characterized for their globule size and <i>ex vivo</i> permeation. The optimized batch was further loaded with RSV and evaluated for in vitro and <i>ex vivo</i> permeation and for in vivo hepatotoxicity. The developed ITT-SNEDDS exhibited globule size below 300 nm, up to 272.27 ± 7.12 mcg/cm².h and 61.27 ± 2.83% of steady-state flux (J_SS) and permeability % respectively. Optimum formulation consisted of 0.15 g oil mixture, 0.6 g of surfactant (Labrasol), and 0.250 g co-surfactant (Transcutol). Permeability studies confirmed the enhanced permeation percentage of ITT (40.77 ± 1.18%), and RSV (29.94 ± 2.02%) from optimized formulation, with enhanced steady-state flux (J_SS). In vivo studies demonstrated the superior hepatoprotective activity of optimized formulation compared to a different drug formulations and marketed product. Therefore, RVS loaded ITT-SNEDDS might be a successful strategy for acne management with improved action, and minimum side effects.

寻常痤疮（Acne Vulgaris）是全球范围内最常见的累及多数青少年的慢性炎症性皮肤疾病之一。异维A酸（Isotretinoin, ITT）是痤疮治疗的首选药物，但口服给药后可引发包括肝毒性在内的严重不良反应，以及部分精神心理异常。本研究旨在开发并优化载异维A酸的自乳化纳米乳（ITT-SNEDDS），并将白藜芦醇（Resveratrol, RSV）纳入最优处方以减轻ITT的不良反应。

首先，本研究考察了ITT在多种精油、表面活性剂及助表面活性剂中的溶解度，以此筛选纳米乳的核心处方成分。采用混料设计考察自变量及其交互作用对选定因变量的影响。对所制备的ITT-SNEDDS进行粒径与离体（ex vivo）渗透特性表征。将最优处方进一步负载RSV，并对其体外（in vitro）、离体渗透特性以及体内（in vivo）肝毒性进行评价。

所制备的ITT-SNEDDS粒径低于300 nm，稳态透皮通量（J_SS）可达272.27±7.12 mcg/cm²·h，渗透百分比可达61.27±2.83%。最优处方组成为：0.15 g油相混合物、0.6 g表面活性剂（Labrasol）与0.250 g助表面活性剂（Transcutol）。渗透研究证实，该最优处方中ITT的渗透百分比可达40.77±1.18%，RSV可达29.94±2.02%，且稳态透皮通量得到显著提升。体内研究表明，与其他药物制剂及市售产品相比，该最优处方展现出更优异的肝保护活性。因此，负载RSV的ITT-SNEDDS有望成为痤疮治疗的有效策略，可提升治疗效果并降低不良反应。