Center for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
J Pharm Sci. 2013 Mar;102(3):1063-75. doi: 10.1002/jps.23446. Epub 2013 Jan 9.
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.
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。