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基于纳米结构脂质载体的纳米凝胶包载他克莫司用于银屑病的持续治疗的制剂开发。

Formulation development of nanostructured lipid carrier-based nanogels encapsulating tacrolimus for sustained therapy of psoriasis.

机构信息

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, India.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, India.

出版信息

Int J Pharm. 2024 Jul 20;660:124172. doi: 10.1016/j.ijpharm.2024.124172. Epub 2024 Apr 26.

Abstract

The goal of this study was to formulate tacrolimus nanogel based on nanostructured lipid carrier (NLC) in order to improve the efficacy, aesthetic, and patient compliance for the treatment of psoriasis. The microemulsion method was used to create phase diagrams and NLCs were prepared using points obtained from the microemulsion region and characterized. The gelling agent carbopol was used to develop an NLC-based nanogel. The pH, drug assay, viscosity, spreadability, and in vitro release of the nanogel, were evaluated. Ex vivo cytotoxicity of the formulation was assessed in murine fibroblast cells. Oxazolone and imiquimod models of psoriasis were used to assess the effectiveness of the nanogel. The NLCs exhibited a submicron particle size of 320 ± 10 nm, a low polydispersity index (<0.3), and a zeta potential of -19.4 mV. Morphological analysis revealed spherical nanoparticles with an encapsulation efficiency of 60 ± 3 %. The nanogel maintained a pH of 6.0 ± 0.5 and possessed a remarkable drug content of 99.73 ± 1.4 %. It exhibited pseudoplastic flow behaviour, ensuring easy spreadability, and demonstrated sustained drug release exceeding 90 % over a 24-hr period. Ex vivo cytotoxicity assessments revealed that the nanogel was safe because no cell death was induced. Nanogel resolved psoriatic blisters, was non-irritating and improved skin elasticity. The favorable properties, safety profile, and remarkable efficacy show the potential of the nanogel as a patient-friendly and effective therapeutic option for psoriasis treatment.

摘要

本研究的目的是基于纳米结构脂质载体(NLC)来制备他克莫司纳米凝胶,以提高治疗银屑病的疗效、美观度和患者顺应性。采用微乳液法绘制相图,并采用微乳液区域获得的点制备 NLC 并进行表征。使用胶凝剂 Carbopol 开发基于 NLC 的纳米凝胶。评价纳米凝胶的 pH 值、药物含量、黏度、铺展性和体外释放。评估制剂在小鼠成纤维细胞中的体外细胞毒性。使用银屑病的氧化唑酮和咪喹莫特模型评估纳米凝胶的有效性。NLC 表现出亚微米粒径为 320±10nm、低多分散指数(<0.3)和 zeta 电位为-19.4mV。形态分析显示出具有 60±3%包封效率的球形纳米粒子。纳米凝胶保持 pH 值为 6.0±0.5,具有显著的药物含量为 99.73±1.4%。它表现出假塑性流动行为,确保易于铺展,并表现出超过 24 小时的 90%以上的持续药物释放。体外细胞毒性评估表明纳米凝胶是安全的,因为没有诱导细胞死亡。纳米凝胶解决了银屑病水疱问题,无刺激性并改善了皮肤弹性。良好的性质、安全特性和显著的疗效表明,纳米凝胶作为一种患者友好且有效的银屑病治疗选择具有潜力。

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