School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, 14040-903, Ribeirao Preto, SP, Brazil.
Division of Dermatology, Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Institute of Physics, University of Sao Paulo, 05508-900, São Paulo, SP, Brazil.
Int J Pharm. 2023 Jun 10;640:123019. doi: 10.1016/j.ijpharm.2023.123019. Epub 2023 May 4.
Liquid crystalline nanoparticles (LCNs) are an attractive drugs topical delivery system due to the great internal ordering, wide interfacial area and structural similarities with the skin. In this work, LCNs were designed to encapsulate triptolide (TP) and to complex on its surface small interfering RNAs (siRNA) targeting TNF-α and IL-6, aiming at topical co-delivery and regulating multi-targets in psoriasis. These multifunctional LCNs showed appropriate physicochemical properties for topical application, such as a mean size of 150 nm, low polydispersion, TP encapsulation greater than 90% and efficient complexation with siRNA. The internal reverse hexagonal mesostructure of LCNs was confirmed by SAXS while their morphology was assessed by cryo-TEM. In vitro permeation studies revealed an increase of more than 20-fold in the distribution of TP through the porcine epidermis/dermis was achieved after the application of LCN-TP or LCN TP in hydrogel. In cell culture, LCNs showed good compatibility and rapid internalization, which was attributed to macropinocytosis and caveolin-mediated endocytosis. Anti-inflammatory potential of multifunctional LCNs was assessed by reducing of TNF-α, IL-6, IL-1β and TGF-β1 levels in LPS-stimulated macrophages. These results support the hypothesis that the co-delivery of TP and siRNAs by LCNs may be a new strategy for psoriasis topical therapy.
液晶纳米颗粒（LCNs）是一种有吸引力的药物局部递药系统，因为它们具有很大的内部有序性、宽的界面面积和与皮肤的结构相似性。在这项工作中，LCNs 被设计用于包裹雷公藤红素（TP），并在其表面复合针对 TNF-α 和 IL-6 的小干扰 RNA（siRNA），旨在局部共递药并调节银屑病中的多靶点。这些多功能 LCNs 表现出适合局部应用的适当物理化学性质，例如平均粒径为 150nm、低多分散性、TP 包封率大于 90%以及与 siRNA 的有效复合。LCNs 的内部反向六方介孔结构通过 SAXS 得到证实，而其形态通过 cryo-TEM 进行评估。体外渗透研究表明，在应用 LCN-TP 或 LCN-TP 在水凝胶中后，通过猪表皮/真皮的 TP 分布增加了 20 多倍。在细胞培养中，LCNs 表现出良好的相容性和快速内化，这归因于巨胞饮和网格蛋白介导的内吞作用。多功能 LCNs 的抗炎潜力通过降低 LPS 刺激的巨噬细胞中 TNF-α、IL-6、IL-1β 和 TGF-β1 的水平来评估。这些结果支持了 LCNs 共递药 TP 和 siRNAs 可能是银屑病局部治疗的新策略的假设。
