Preparation and characterisation of esculetin-loaded nanostructured lipid carriers gels for topical treatment of UV-induced psoriasis

As an inflammatory and autoimmune skin condition, psoriasis affects 2–3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilised to treat psoriasis. The goal of this work is to improve Esc’s solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increasing the residence time on the skin which infers better skin absorption The particle size, zeta potential and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption and residence time on the skin. Esc NLC gels were evaluated by <i>in vitro</i> release and <i>in vivo</i> effectiveness on a rat model of UV-induced psoriasis. Esc NLCs showed high EE reaching more than 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11 nm) and were spherical. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. Compared to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis. As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis.

作为一种炎症性自身免疫性皮肤病，银屑病（psoriasis）在全球范围内影响2%~3%的人群。银屑病患者需长期接受免疫抑制药物治疗，而此类药物存在严重不良反应。七叶亭（Esculetin，Esc）是一种已被用于治疗银屑病的天然药物。本研究旨在通过开发新型七叶亭纳米结构脂质载体（nanostructured lipid carriers，NLCs），改善Esc的溶解性以用于银屑病治疗，并延长其在皮肤中的滞留时间，进而提升皮肤吸收效率。
本研究对Esc NLCs的粒径、zeta电位（zeta potential）与包封率（entrapment efficiency，EE）进行了评估。将NLCs掺入阿拉伯胶凝胶制剂中，可提升其工业应用性、皮肤吸收性与皮肤滞留时间。
Esc NLC凝胶通过体外（in vitro）释放实验与体内（in vivo）UV诱导银屑病大鼠模型的药效评价进行了考察。Esc NLCs的包封率可达95%以上，粒径范围为(53.86±0.38~236.3±0.11) nm，且呈球形形貌。
Esc NLC凝胶的释放研究显示，Esc呈现快速释放特征，提示其生物利用度得到提升。与游离Esc相比，Esc NLC凝胶（F2）可显著降低皮肤中CD34与TNF-α的表达水平。该结果通过组织病理学分析得到验证。鉴于Esc NLC凝胶（F2）具有强效抗炎特性，本研究结果表明其在银屑病治疗中具备显著的应用潜力。