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使用可溶性微针进行铁的透皮给药:皮肤动力学与安全性

Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety.

作者信息

Modepalli Naresh, Shivakumar H Nanjappa, McCrudden Maeliosa T C, Donnelly Ryan F, Banga Ajay, Murthy S Narasimha

机构信息

The University of Mississippi School of Pharmacy, Mississippi 38677.

Institute for Drug Delivery and Biomedical Research, Bangalore, India; KLE's University College of Pharmacy, Bangalore, India.

出版信息

J Pharm Sci. 2016 Mar;105(3):1196-200. doi: 10.1016/j.xphs.2015.12.008.

Abstract

Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy.

摘要

目前,铁化合物通过口服和肠胃外途径用于各年龄段患者,以治疗缺铁症。尽管通过这些传统途径补充铁的工作一直在持续进行,但缺铁仍然是全球最普遍的营养失调症。经皮补充铁是一种新型的、有潜力的补铁方法。焦磷酸铁(FPP)被发现是经皮补充铁的合适铁源。在本项目中,通过用高浓度FPP刺激皮肤成纤维细胞来评估FPP的安全性。进行了细胞活力测定和活性氧测定。开发了可溶性微针阵列,将其与FPP以及皮肤中游离铁的动力学相结合;在无毛大鼠中研究了微针阵列经皮给药后皮肤细胞外液中的情况。从基于细胞的测定结果来看,FPP被选为经皮递送的潜在铁源之一。发现微针在给药后3小时内可溶解于皮肤液中。微针阵列完全溶解后,皮肤细胞外液中的FPP浓度下降。总体而言,这些研究证明了FPP用于皮肤给药的安全性以及可溶性微针方法用于经皮补铁治疗的可行性。

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