Alam Meraj, Rizwanullah Md, Ahmad Shahnawaz, Iqubal Ashif, Mir Showkat R, Kim Tae-Geum, Amin Saima
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, 140401, Punjab, India.
AAPS PharmSciTech. 2025 Mar 26;26(4):90. doi: 10.1208/s12249-025-03074-y.
Psoriasis is a chronic inflammatory skin disorder affecting 2-5% of the global population and is often characterized by skin thickening, scaling, and various epidermal changes. Current topical treatments have limitations in terms of efficacy, skin penetration, and side effects. The present study aimed to develop a novel nanostructured lipid carrier (NLC) gel that co-encapsulates tacrolimus (TAC) and thymoquinone (THQ) to enhance drug delivery and efficacy in the treatment of psoriasis. TAC-THQ-NLC was formulated using the emulsification solvent-evaporation technique and subsequently converted into nanogel using Carbopol Ultrez10 as a gelling agent. The prepared nanogel efficacy was evaluated through ex-vivo skin permeation, dermatokinetic analysis, and psoriasis-induced Balb/c mice model. The TAC-THQ-NLC-gel (TAC-THQ-NG) demonstrated significantly higher skin permeation compared to the TAC-THQ-suspension-gel (TAC-THQ-SG). Specifically, the permeation enhancement for the NLC-gel was 2.51-fold and 2.12-fold for TAC and THQ, respectively. These enhancements were confirmed using Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). The dermatokinetic analysis showed that the TAC-THQ-NG had 2.78-fold and 2.37-fold higher maximum concentration (C) and 2.93-fold and 2.40-fold higher area under the curve (AUC) for TAC and THQ, respectively, compared to the TAC-THQ-SG. Further, in the Balb/c mice psoriasis model, the TAC-THQ-NG formulation resulted in an 83.80 ± 3.62% reduction in the cumulative Psoriasis Area Severity Index (PASI) score of thickness, erythema, and scaling, compared to the TAC-THQ-SG formulation, which showed 57 ± 9.90% reduction. The results of the in vivo skin compliance study suggested that the developed TAC-THQ-NG was safe for topical application. Further histopathological examination showed no significant changes in the skin, spleen, and liver, indicating the efficacy and safety of the TAC-THQ-NG formulation. Based on these observations, it can be inferred that the developed TAC-THQ-NG exhibits superior therapeutic efficacy.
银屑病是一种慢性炎症性皮肤病，影响全球2%-5%的人口，其特征通常为皮肤增厚、脱屑以及各种表皮变化。目前的局部治疗在疗效、皮肤渗透性和副作用方面存在局限性。本研究旨在开发一种新型纳米结构脂质载体（NLC）凝胶，该凝胶共包封他克莫司（TAC）和百里醌（THQ），以提高银屑病治疗中的药物递送和疗效。采用乳化溶剂蒸发技术制备TAC-THQ-NLC，随后使用卡波姆Ultrez10作为胶凝剂将其转化为纳米凝胶。通过体外皮肤渗透、皮肤动力学分析和银屑病诱导的Balb/c小鼠模型评估所制备纳米凝胶的疗效。与TAC-THQ悬浮凝胶（TAC-THQ-SG）相比，TAC-THQ-NLC凝胶（TAC-THQ-NG）表现出显著更高的皮肤渗透性。具体而言，NLC凝胶对TAC和THQ的渗透增强倍数分别为2.51倍和2.12倍。使用傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）证实了这些增强效果。皮肤动力学分析表明，与TAC-THQ-SG相比，TAC-THQ-NG的TAC和THQ的最大浓度（C）分别高2.78倍和2.37倍，曲线下面积（AUC）分别高2.93倍和2.40倍。此外，在Balb/c小鼠银屑病模型中，与显示降低57±9.90%的TAC-THQ-SG制剂相比，TAC-THQ-NG制剂使厚度、红斑和脱屑的银屑病面积严重程度指数（PASI）累积评分降低了83.80±3.62%。体内皮肤顺应性研究结果表明，所开发的TAC-THQ-NG局部应用是安全的。进一步的组织病理学检查显示皮肤、脾脏和肝脏无明显变化，表明TAC-THQ-NG制剂的疗效和安全性。基于这些观察结果，可以推断所开发的TAC-THQ-NG具有优异的治疗效果。
