Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by intense itching and recurrent eczematous lesions. Topical corticosteroids are the first-line treatment to control moderate-to-severe AD; however, prolonged application of corticosteroids is required, which can result in dermal atrophy as a side effect. Drug-delivery systems can provide more effective and targeted therapy strategies. In this study, budesonide (BUD) was encapsulated into chitosan (CS)-coated PLGA nanoparticles, which were further incorporated into poloxamer hydrogels to improve the anti-inflammatory activity and decrease adverse effects. The nanoparticles were prepared by the emulsification–solvent evaporation technique, and their physicochemical characteristics were evaluated. Rheological properties of the hydrogels, such as viscosity and sol–gel transition temperature, were evaluated with and without nanoparticles. In vitro release kinetics and ex vivo drug absorption studies were performed using Franz diffusion cells. The nanoparticles showed a mean diameter of 324 ± 4 nm, positive ζ potential (20 mV) due to CS coating, and high encapsulation efficiency (>90%). The nanoparticles did not show cytotoxic effects in primary human fibroblasts and keratinocytes; however, all formulations induced the generation of reactive oxygen species. Both nanoparticles and hydrogels were able to change the release kinetics of BUD when compared to the nonencapsulated compound. Nanoparticles were not able to surmount the stratum corneum of excised human skin, but the nanoencapsulation facilitated the skin absorption of BUD. The hydrogels containing nanoparticles or not showed non-Newtonian and pseudoplastic behavior. The nanoformulations seem to be a good candidate to deliver glucocorticoids in the skin of AD patients.

中文翻译：

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含有布地奈德纳米颗粒的水凝胶促进特应性皮炎治疗应用的经皮吸收

特应性皮炎 (AD) 是一种慢性、复发性炎症性皮肤病，其特征是剧烈瘙痒和复发性湿疹病变。外用皮质类固醇是控制中重度 AD 的一线治疗方法；然而，需要长时间使用皮质类固醇，这可能会导致皮肤萎缩作为副作用。给药系统可以提供更有效和更有针对性的治疗策略。在这项研究中，布地奈德 (BUD) 被封装到壳聚糖 (CS) 包覆的 PLGA 纳米粒子中，然后将其进一步掺入泊洛沙姆水凝胶中，以提高抗炎活性并减少不良反应。通过乳化-溶剂蒸发技术制备纳米颗粒，并评估其理化特性。水凝胶的流变特性，例如粘度和溶胶-凝胶转变温度，在有和没有纳米颗粒的情况下进行了评估。使用 Franz 扩散池进行体外释放动力学和离体药物吸收研究。纳米粒子的平均直径为 324 ± 4 nm，由于 CS 涂层而具有正 ζ 电位 (20 mV)，以及高封装效率 (> 90%)。纳米颗粒在原代人成纤维细胞和角质形成细胞中没有显示细胞毒性作用；然而，所有配方都会诱导活性氧的产生。与未包封的化合物相比，纳米颗粒和水凝胶都能够改变 BUD 的释放动力学。纳米颗粒无法超越人体皮肤角质层，但纳米胶囊促进了 BUD 的皮肤吸收。含有或不含有纳米颗粒的水凝胶表现出非牛顿和假塑性行为。纳米制剂似乎是在 AD 患者皮肤中输送糖皮质激素的良好候选者。