Nene Shweta, Devabattula Geetanjali, Vambhurkar Ganesh, Tryphena Kamatham Pushpa, Khatri Dharmendra Kumar, Godugu Chandraiah, Singh Pankaj Kumar, Srivastava Saurabh
Pharmaceutical Innovation and Translational Research Lab (PITRL), Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India.
Drug Deliv Transl Res. 2025 Jun;15(6):2200-2219. doi: 10.1007/s13346-024-01732-5. Epub 2024 Oct 28.
Baricitinib, an inhibitor of Janus kinase 1/2 receptors majorly involved in the dysregulation of immune responses in atopic dermatitis, is currently approved for managing atopic dermatitis in Europe. The delivery of baricitinib through oral route is associated to several adverse effects due to off-target effects. Therefore, the current study is aimed at formulation of baricitinib loaded nanoemulgel for evaluation of topical delivery potential in the treatment of atopic dermatitis. The baricitinib-loaded nanoemulsions (0.05 and 0.1% w/w) revealed an average globule size of 162.86 ± 0.37 and 173.66 ± 4.88 nm respectively with narrow PDI. The optimized batch of baricitinib nanoemulsion was converted to nanoemulgel by the addition of the mixture of gel bases SEPINEO™ DERM and SEPINEO™ P 600 along with propylene glycol, resulting in pseudoplastic shear thinning behaviour. The optimized nanoemulgels have shown prominent retention of baricitinib in the skin along with permeation. The skin distribution study of coumarin-6 loaded nanoemulgel demonstrated high fluorescence in the epidermal layer. The western blot analysis revealed significant inhibition of phosphorylated signal transducers and activators of transcriptions 1 (##p < 0.01) and 3 (#p < 0.05) by application of 0.05 and 0.1% baricitinib nanoemulgel. The baricitinib nanoemulgels have shown anti-inflammatory activity by significantly reducing expressions of various inflammatory markers. Histopathological analysis of skin tissues treated with baricitinib nanoemulgel has demonstrated a marked reduction in acanthosis, hyperkeratosis, and intact outer epidermis. These results supported the potential role of baricitinib-loaded nanoemulgel in reducing the inflammation and disease severity associated with atopic dermatitis.
巴瑞替尼是一种主要参与特应性皮炎免疫反应失调的Janus激酶1/2受体抑制剂，目前在欧洲被批准用于治疗特应性皮炎。由于脱靶效应，通过口服途径给药的巴瑞替尼会产生多种不良反应。因此，本研究旨在制备负载巴瑞替尼的纳米乳凝胶，以评估其在治疗特应性皮炎中的局部给药潜力。负载巴瑞替尼的纳米乳剂（0.05%和0.1% w/w）的平均球粒尺寸分别为162.86±0.37和173.66±4.88nm，多分散指数较窄。通过添加凝胶基质SEPINEO™ DERM和SEPINEO™ P 600的混合物以及丙二醇，将优化后的巴瑞替尼纳米乳剂批次转化为纳米乳凝胶，从而产生假塑性剪切变稀行为。优化后的纳米乳凝胶显示出巴瑞替尼在皮肤中的显著保留以及渗透。负载香豆素-6的纳米乳凝胶的皮肤分布研究表明，表皮层具有高荧光。蛋白质免疫印迹分析显示，应用0.05%和0.1%的巴瑞替尼纳米乳凝胶可显著抑制磷酸化转录信号转导子和激活子1（##p<0.01）和3（#p<0.05）。巴瑞替尼纳米乳凝胶通过显著降低各种炎症标志物的表达而显示出抗炎活性。用巴瑞替尼纳米乳凝胶处理的皮肤组织的组织病理学分析表明，棘皮症、角化过度明显减轻，表皮外层完整。这些结果支持了负载巴瑞替尼的纳米乳凝胶在减轻与特应性皮炎相关的炎症和疾病严重程度方面的潜在作用。
