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脂质体布地奈德在实验性哮喘中的疗效

Efficacy of liposomal budesonide in experimental asthma.

作者信息

Konduri Kameswari S, Nandedkar Sandhya, Düzgünes Nejat, Suzara Vincent, Artwohl James, Bunte Ralph, Gangadharam Pattisapu R J

机构信息

Department of Pediatrics, Medical College of Wisconsin, 9000 West Wisconsin Avenue, PO Box 1997, Milwaukee, WI 53201, USA.

出版信息

J Allergy Clin Immunol. 2003 Feb;111(2):321-7. doi: 10.1067/mai.2003.104.

Abstract

BACKGROUND

Inhaled corticosteroids, such as budesonide, attenuate the inflammatory response in asthma. However, patient noncompliance and side effects of available inhaled corticosteroids limit their use. Liposomes are currently used in medicine to deliver a variety of drugs.

OBJECTIVE

The objective of our study was to determine whether weekly therapy with budesonide encapsulated in sterically stabilized (stealth) liposomes would be comparable to daily budesonide therapy in reducing allergic inflammation.

METHODS

Ovalbumin-sensitized C57/Black 6 mice received aerosolized (1) budesonide encapsulated in stealth or conventional liposomes, administered weekly, (2) budesonide (without liposomes), administered either daily or weekly, or (3) empty stealth liposomes, administered weekly. All treatment groups were compared with sensitized untreated or unsensitized mice. Histopathologic examination of the lung tissues and measurements of eosinophil peroxidase activity, peripheral blood eosinophil counts, and total serum IgE levels were done weekly for 4 weeks.

RESULTS

Weekly therapy with budesonide encapsulated in stealth liposomes was as effective as daily budesonide therapy in decreasing lung inflammation and lowering eosinophil peroxidase activity, peripheral blood eosinophils, and total serum IgE levels. In none of the other groups was there a significant decrease in the inflammatory parameters evaluated.

CONCLUSION

We conclude that weekly therapy with budesonide encapsulated in stealth liposomes is as effective as daily budesonide in reducing markers of lung inflammation in experimental asthma. This novel strategy offers an effective alternative to standard daily budesonide therapy in asthma and has the potential to reduce toxicity and improve compliance.

摘要

背景

吸入性糖皮质激素,如布地奈德,可减轻哮喘中的炎症反应。然而,患者的不依从性以及现有吸入性糖皮质激素的副作用限制了它们的使用。脂质体目前在医学上用于递送多种药物。

目的

我们研究的目的是确定每周使用包裹在空间稳定(隐形)脂质体中的布地奈德进行治疗,在减轻过敏性炎症方面是否与每日使用布地奈德治疗效果相当。

方法

用卵清蛋白致敏的C57/黑6小鼠接受雾化吸入:(1)包裹在隐形或常规脂质体中的布地奈德,每周给药一次;(2)布地奈德(无脂质体),每日或每周给药一次;或(3)空的隐形脂质体,每周给药一次。将所有治疗组与致敏未治疗或未致敏的小鼠进行比较。对肺组织进行组织病理学检查,并每周测量嗜酸性粒细胞过氧化物酶活性、外周血嗜酸性粒细胞计数和血清总IgE水平,持续4周。

结果

每周使用包裹在隐形脂质体中的布地奈德进行治疗,在减轻肺部炎症、降低嗜酸性粒细胞过氧化物酶活性、外周血嗜酸性粒细胞和血清总IgE水平方面,与每日使用布地奈德治疗效果相同。在其他组中,所评估炎症参数均未出现显著下降。

结论

我们得出结论,每周使用包裹在隐形脂质体中的布地奈德进行治疗,在减轻实验性哮喘肺部炎症标志物方面与每日使用布地奈德效果相同。这种新策略为哮喘标准每日布地奈德治疗提供了一种有效的替代方法,并且有可能降低毒性并提高依从性。

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