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作为氢化可的松控释载体的生物聚合物薄膜:治疗慢性皮肤病的有前景的装置。

Biopolymeric films as delivery vehicles for controlled release of hydrocortisone: Promising devices to treat chronic skin diseases.

作者信息

Voss Guilherme T, Gularte Matheus S, de Oliveira Renata L, Luchese Cristiane, Fajardo André R, Wilhelm Ethel A

机构信息

Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Universidade Federal de Pelotas (UFPel), Campus Capão do Leão, 96010-900 Pelotas, RS, Brazil.

Laboratório de Tecnologia e Desenvolvimento de Compósitos e Materiais Poliméricos (LaCoPol), Universidade Federal de Pelotas (UFPel), Campus Capão do Leão s/n, 96010-900 Pelotas, RS, Brazil.

出版信息

Mater Sci Eng C Mater Biol Appl. 2020 Sep;114:111074. doi: 10.1016/j.msec.2020.111074. Epub 2020 May 11.

Abstract

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with nasty effects on the psychosocial wellbeing of patients. Overall, glucocorticoids, such as hydrocortisone (HC), are the primary pharmacologic drugs used to treat AD and its symptoms. However, the long-term treatment with HC is often accompanied by severe adverse effects. So, this study reports the encapsulation of HC in polymeric films based on gelatin (Gel) and gelatin/starch (Gel/St) and investigates their potential to treat and attenuate 2,4-Dinitrochlorobenzene (DNCB)-induced AD-like symptoms in BALB/c mice model. The prepared films were characterized by different techniques, which indicated that HC was physically entrapped into the polymer matrices. In vitro experiments indicate that the HC release process occurs in a controlled manner (up to 48 h) for both films. Regarding the in vivo experiments, HC-loaded films (Gel@HC and Gel/St@HC), unloaded films (Gel and Gel/St) and HC cream (1%) (as reference) were applied topically on the back of the DNCB-sensitized animals and skin severity scores and scratching behavior were determined. Ex-vivo experiments were done to quantify inflammatory and/or biochemical parameters. As assessed, the topical application of the biopolymeric films (loaded or not with HC) improved the inflammatory parameters, while a lower corticosterone level was observed for the animals treated with Gel and Gel@HC films. In summary, the HC-loaded films showed superior efficiency to treat/attenuate the analyzed parameter than the HC cream (1%). Further, no death or sign of toxicity was observed in animals exposed to HC-loaded films. Thus, the encapsulation of HC in biopolymeric films seems to be a promising alternative for the treatment of injuries caused by chronic skin diseases that require prolonged use of glucocorticoids.

摘要

特应性皮炎(AD)是最常见的慢性炎症性皮肤病,对患者的心理社会福祉有不良影响。总体而言,糖皮质激素,如氢化可的松(HC),是用于治疗AD及其症状的主要药物。然而,长期使用HC治疗往往伴随着严重的不良反应。因此,本研究报道了将HC封装在基于明胶(Gel)和明胶/淀粉(Gel/St)的聚合物薄膜中,并研究它们在BALB/c小鼠模型中治疗和减轻2,4-二硝基氯苯(DNCB)诱导的类AD症状的潜力。通过不同技术对制备的薄膜进行了表征,结果表明HC被物理包裹在聚合物基质中。体外实验表明,两种薄膜的HC释放过程均以可控方式进行(长达48小时)。关于体内实验,将负载HC的薄膜(Gel@HC和Gel/St@HC)、未负载的薄膜(Gel和Gel/St)和HC乳膏(1%)(作为对照)局部应用于DNCB致敏动物的背部,并测定皮肤严重程度评分和抓挠行为。进行了体外实验以量化炎症和/或生化参数。经评估,生物聚合物薄膜(负载或未负载HC)的局部应用改善了炎症参数,而用Gel和Gel@HC薄膜治疗的动物的皮质酮水平较低。总之,负载HC的薄膜在治疗/减轻分析参数方面显示出比HC乳膏(1%)更高的效率。此外,在接触负载HC薄膜的动物中未观察到死亡或毒性迹象。因此,将HC封装在生物聚合物薄膜中似乎是治疗需要长期使用糖皮质激素的慢性皮肤病所致损伤的一种有前景的替代方法。

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