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IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2025-03-26 DOI:10.1208/s12249-025-03074-y

Meraj Alam, Md. Rizwanullah, Shahnawaz Ahmad, Ashif Iqubal, Showkat R. Mir, Tae-Geum Kim, Saima Amin

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引用次数: 0

摘要

牛皮癣是一种慢性炎症性皮肤病，影响着全球 2%-5% 的人口，通常以皮肤增厚、脱屑和各种表皮变化为特征。目前的外用治疗方法在疗效、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，该凝胶可共同包裹他克莫司（TAC）和胸腺醌（THQ），以增强药物的输送和治疗银屑病的疗效。TAC-THQ-NLC 采用乳化溶剂-蒸发技术配制，随后使用 Carbopol Ultrez10 作为胶凝剂转化为纳米凝胶。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，对制备的纳米凝胶进行了药效评估。与TAC-THQ-悬浮凝胶（TAC-THQ-SG）相比，TAC-THQ-NLC-凝胶（TAC-THQ-NG）的皮肤渗透率明显更高。具体来说，NLC-凝胶对 TAC 和 THQ 的渗透率分别提高了 2.51 倍和 2.12 倍。傅立叶变换红外光谱法（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 的最大浓度（Cmax）分别高出 2.78 倍和 2.37 倍，曲线下面积（AUC）分别高出 2.93 倍和 2.40 倍。此外，在 Balb/c 小鼠银屑病模型中，与 TAC-THQ-SG 制剂相比，TAC-THQ-NG 制剂在厚度、红斑和鳞屑方面的累积银屑病面积严重性指数（PASI）得分降低了 83.80 ± 3.62%，而 TAC-THQ-SG 制剂则降低了 57 ± 9.90%。体内皮肤顺应性研究结果表明，所开发的 TAC-THQ-NG 可以安全地用于局部治疗。进一步的组织病理学检查显示，皮肤、脾脏和肝脏均无明显变化，表明 TAC-THQ-NG 制剂的有效性和安全性。基于这些观察结果，可以推断所开发的 TAC-THQ-NG 具有卓越的疗效。

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Co-Delivery of Tacrolimus and Thymoquinone Topically by Nanostructured Lipid Carrier Gel for Enhanced Efficacy Against Psoriasis

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_max) 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.

Graphical Abstract

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.