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水凝胶作为壳聚糖纳米载体的抗皮炎作用:使用 NC/Nga 小鼠模型的体外和体内评估。

Antidermatitic perspective of hydrocortisone as chitosan nanocarriers: an ex vivo and in vivo assessment using an NC/Nga mouse model.

机构信息

Center for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.

出版信息

J Pharm Sci. 2013 Mar;102(3):1063-75. doi: 10.1002/jps.23446. Epub 2013 Jan 9.

DOI:10.1002/jps.23446
PMID:23303620
Abstract

The aim of this study to administer hydrocortisone (HC) percutaneously in the form of polymeric nanoparticles (NPs) to alleviate its transcutaneous absorption, and to derive additional wound-healing benefits of chitosan. HC-loaded NPs had varied particle sizes, zeta potentials, and entrapment efficiencies, when drug-to-polymer mass ratios increased from 1:1 to 1:8. Ex vivo permeation analysis showed that the nanoparticulate formulation of HC significantly reduced corresponding flux [∼24 µg/(cm(2) h)] and permeation coefficient (∼4.8 × 10(-3) cm/h) of HC across the full thickness NC/Nga mouse skin. The nanoparticulate formulation also exhibited a higher epidermal (1610 ± 42 µg/g of skin) and dermal (910 ± 46 µg/g of skin) accumulation of HC than those associated with control groups. An in vivo assessment using an NC/Nga mouse model further revealed that mice treated with the nanoparticulate system efficiently controlled transepidermal water loss [15 ± 2 g/(m(2) h)], erythema intensity (232 ± 12), dermatitis index (mild), and thickness of skin (456 ± 27 µm). Taken together, histopathological examination predicted that the nanoparticulate system showed a proficient anti-inflammatory and antifibrotic activity against atopic dermatitic (AD) lesions. Our results strongly suggest that HC-loaded NPs have promising potential for topical/transdermal delivery of glucocorticoids in the treatment of AD.

摘要

本研究旨在通过聚合物纳米粒子(NPs)的形式经皮给予氢化可的松(HC),以减轻其经皮吸收,并获得壳聚糖的额外伤口愈合益处。当药物与聚合物的质量比从 1:1 增加到 1:8 时,HC 负载的 NPs 具有不同的粒径、Zeta 电位和包封效率。体外渗透分析表明,HC 的纳米颗粒制剂显著降低了相应的通量[约 24 µg/(cm²h)]和 HC 穿过全厚度 NC/Nga 小鼠皮肤的渗透系数(约 4.8×10(-3) cm/h)。纳米颗粒制剂还表现出比对照组更高的 HC 表皮(1610±42 µg/g 皮肤)和真皮(910±46 µg/g 皮肤)积累。使用 NC/Nga 小鼠模型进行的体内评估进一步表明,用纳米颗粒系统治疗的小鼠有效地控制了经表皮水分流失[15±2 g/(m²h)]、红斑强度(232±12)、皮炎指数(轻度)和皮肤厚度(456±27 µm)。总的来说,组织病理学检查预测纳米颗粒系统对特应性皮炎(AD)病变具有有效的抗炎和抗纤维化活性。我们的结果强烈表明,HC 负载的 NPs 具有在治疗 AD 中局部/经皮递送糖皮质激素的巨大潜力。

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