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用于改善银屑病的双靶点纳米乳凝胶的体外和体内研究

In Vitro and In Vivo Investigation of a Dual-Targeted Nanoemulsion Gel for the Amelioration of Psoriasis.

作者信息

Khan Rahmuddin, Mirza Mohd Aamir, Aqil Mohd, Alex Thomson Santosh, Raj Nafis, Manzoor Nikhat, Naseef Punnoth Poonkuzhi, Saheer Kuruniyan Mohamed, Iqbal Zeenat

机构信息

Department of Pharmaceutics, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi 110062, India.

Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.

出版信息

Gels. 2023 Jan 28;9(2):112. doi: 10.3390/gels9020112.

Abstract

Psoriasis, due to its unique pathological manifestations and the limited success of existing therapeutic modalities, demands dedicated domain research. Our group has developed nanotherapeutics consisting of bioactives such as Thymoquinone (TQ) and Fulvic acid (FA), which have been successfully incorporated into a Nanoemulsion gel (NEG), taking kalonji oil as oil phase. The composition is aimed at ameliorating psoriasis with better therapeutic outcomes. TQ is a natural bio-active that has been linked to anti-psoriatic actions. FA has anti-inflammatory actions due to its free radical and oxidant-scavenging activity. Our previous publication reports the formulation development of the NEG, where we overcame the pharmaco-technical limitations of combining the above two natural bioactives. In vitro evaluation of the optimized NEG was carried out, which showed an enhanced dissolution rate and skin permeation of TQ. This work furthers the pharmaceutical progression of dual-targeted synergistic NEG to treat psoriasis. A suitable animal model, BALB/c mice, has been used to conduct the in vivo studies, which revealed the effective anti-psoriatic action of TQ. Molecular docking studies corroborated the results and revealed a good binding affinity for both the targets of TNF-α (Tumor necrosis factor) and IL-6 (Interlukin-6). Tissue uptake by Confocal laser scanning microscopy (CLSM), a skin interaction study of the gel formulation, and an antioxidant free radical scavenging assay (1-1 Diphenyl-2-picrylhydrazyl DPPH) were also carried out. It was concluded that the NEG may be effective in treating psoriasis with minimal side effects.

摘要

银屑病因其独特的病理表现以及现有治疗方式成效有限,需要专门的领域研究。我们团队研发了一种纳米疗法,其包含百里醌(TQ)和富里酸(FA)等生物活性成分,这些成分已成功被纳入纳米乳液凝胶(NEG)中,以黑种草籽油作为油相。该组合物旨在改善银屑病并取得更好的治疗效果。TQ是一种天然生物活性物质,已被证实与抗银屑病作用有关。FA因其自由基和抗氧化清除活性而具有抗炎作用。我们之前的出版物报道了NEG的制剂研发,在其中我们克服了将上述两种天然生物活性成分组合时的药学技术限制。对优化后的NEG进行了体外评估,结果显示TQ的溶出速率和皮肤渗透率均有所提高。这项工作进一步推动了用于治疗银屑病的双靶点协同纳米乳液凝胶的药学进展。已使用合适的动物模型BALB/c小鼠进行体内研究,结果显示TQ具有有效的抗银屑病作用。分子对接研究证实了这些结果,并揭示了对肿瘤坏死因子(TNF-α)和白细胞介素-6(IL-6)这两个靶点都具有良好的结合亲和力。还进行了共聚焦激光扫描显微镜(CLSM)的组织摄取、凝胶制剂的皮肤相互作用研究以及抗氧化自由基清除试验(1,1-二苯基-2-苦基肼基,DPPH)。得出的结论是,纳米乳液凝胶可能在治疗银屑病方面有效且副作用最小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479f/9957534/9af88b1fbd1a/gels-09-00112-g001.jpg

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