Purpose: Psoriasis is an inflammatory skin disease, where keratinocytes play pivotal roles in its pathogenesis. We prepared Celastrol Noisome hydrogel (Cel Nio gel) for the treatment of psoriasis and aimed to study its target site as well as the mechanism.
Methods: Cel Nio was fabricated with thin-film hydration and sonication, then topically administered to imiquimod (IMQ)-induced psoriasis mice. The concentrations of Cel in the skin, blood and lymphatic system were determined using LC-MS. The anti-psoriasis effect of Cel Nio gel was studied, and the levels of inflammatory cytokines in blood were evaluated by flow cytometry. For the in vitro study, the uptake of Nio by HaCaT cells was quantified with flow cytometry, and the anti-inflammatory effect of Cel on HaCaT cells was detected with qPCR. The expressions of inflammatory factors and Ki-67 in skin were observed by immunofluorescence.
Results: Cel Nio possessed a particle size of 133 nm with encapsulation efficacy (EE%) of 83.2%. After topical administration of Cel Nio gel to mice, Cel was mainly accumulated in the skin instead of exposure in blood or lymphatic system, while the levels of inflammatory factors in blood had a significant decline. In addition, the preparation of Nio enhanced the uptake by HaCaT cells, and Cel obviously reduced the mRNA levels of inflammatory cytokines in HaCaT cells. Moreover, Cel Nio gel significantly decreased the expression of inflammatory cytokines and Ki-67 in the skin.
Conclusion: Cel Nio gel achieved the anti-psoriatic effect by inhibiting the inflammation and hyperproliferation of keratinocytes in the skin and further suppressing the systemic inflammation, thus could be a novel topical drug delivery system to treat psoriasis with topical and systemic effects.

Keywords: psoriasis, celastrol niosome, topical delivery, keratinocytes, pharmacokinetics


中文翻译：

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Celastrol Niosome 水凝胶对银屑病小鼠的皮肤角质形成细胞和循环具有抗炎作用，无需全身药物暴露

目的：银屑病是一种炎症性皮肤病，其中角质形成细胞在其发病机制中起关键作用。我们制备了用于治疗银屑病的 Celastrol Noisome 水凝胶（Cel Nio 凝胶），旨在研究其作用部位及其作用机制。
方法：Cel Nio 采用薄膜水合和超声处理制造，然后局部给药于咪喹莫特 (IMQ) 诱导的银屑病小鼠。使用 LC-MS 测定皮肤、血液和淋巴系统中的 Cel 浓度。研究了Cel Nio凝胶的抗银屑病作用，并通过流式细胞仪评估了血液中炎性细胞因子的水平。对于体外研究，通过流式细胞术定量 HaCaT 细胞对 Nio 的摄取，并通过 qPCR 检测 Cel 对 HaCaT 细胞的抗炎作用。免疫荧光法观察皮肤炎症因子和Ki-67的表达。
结果：Cel Nio 的粒径为 133 nm，包封率 (EE%) 为 83.2%。Cel Nio凝胶对小鼠局部给药后，Cel主要在皮肤中积累，而不是暴露在血液或淋巴系统中，而血液中的炎症因子水平明显下降。此外，Nio 的制备增强了 HaCaT 细胞的摄取，而 Cel 明显降低了 HaCaT 细胞中炎性细胞因子的 mRNA 水平。此外，Cel Nio 凝胶显着降低皮肤中炎性细胞因子和 Ki-67 的表达。
结论：Cel Nio 凝胶通过抑制皮肤角质形成细胞的炎症和过度增殖，进一步抑制全身炎症，从而达到抗银屑病的作用，因此可以成为一种具有局部和全身作用的治疗银屑病的新型局部给药系统。

关键词:银屑病, celastrol niosome, 局部给药, 角质形成细胞, 药代动力学