Microneedle and iontophoresis mediated delivery of methotrexate into and across healthy and psoriatic skin.

Microneedle and iontophoresis mediated delivery of methotrexate into and across healthy and psoriatic skin.
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DOI:
10.1016/j.ijpharm.2022.121693
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发表时间:
2022-04-25
影响因子:
5.8
通讯作者:
Banga, Ajay K.
Banga, Ajay K.
中科院分区:
医学2区
文献类型:
--
作者:
Vora, Deepal;Garimella, Harsha T.;German, Carrie L.;Banga, Ajay K.

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牛皮癣是一种皮肤状况,涉及鳞屑、干斑和炎症。甲氨蝶呤(logP:−1.8,相对分子质量:454.44克/摩尔)用于口服或静脉注射治疗银屑病。经皮给药可避免首过代谢和全身毒性。使用全层健康人体皮肤,单独和联合使用离子导入和微针对甲氨蝶呤进行了局部和经皮给药研究。评估进入受损/患病皮肤和穿过受损/患病皮肤的释放也同样相关。因此,本研究使用体外健康和银屑病患者的皮肤来研究甲氨蝶呤的给药情况,以了解皮肤病状况对甲氨蝶呤经皮给药的影响。银屑病患者皮肤的低阻力和高TEWL表明屏障功能受损,而组织学研究表明上皮过度增殖和网脊延长。使用优化的离子导入参数,银屑病患者皮肤的受体递送(39.51±4.45μg/平方厘米)与健康皮肤(43.15±0.83μg/平方厘米)相比无显著差异。然而,甲氨蝶呤在银屑病患者皮肤中的释放量(126.23±24.65μg/平方厘米)显著高于健康皮肤(12.02±4.89μg/平方厘米)。因此,从银屑病患者皮肤中观察到的总输出量显著高于健康皮肤。
Psoriasis is a condition of the skin which involves scales, dry patches, and inflammation. Methotrexate (logP: −1.8, MW:454.44g/mol) is administered orally or intravenously to treat psoriasis. The first-pass metabolism and systemic toxicity can be avoided by administration via skin. Topical and transdermal delivery of methotrexate using iontophoresis and microneedles, alone and in combination was investigated using full-thickness healthy human skin. It is also equally relevant to evaluate the delivery into and across damaged/diseased skin. Hence, this study investigated the delivery of methotrexate using ex vivo healthy and psoriatic human skin to understand the effect of skin disease condition on delivery of methotrexate via skin. A lower resistance and a higher TEWL for psoriatic skin indicated damaged barrier function, while histology studies indicated epithelial hyperproliferation and elongated rete ridges. Using the optimized iontophoretic parameters, there was no significant difference in receptor delivery for psoriatic skin (39.51±4.45μg/sq.cm) as compared to healthy skin (43.15±0.83μg/sq.cm). However, methotrexate delivery into psoriatic skin (126.23±24.65μg/sq.cm) was significantly higher as compared to healthy skin (12.02±4.89μg/sq.cm). Thus, significantly higher total delivery was observed from psoriatic skin than healthy skin.
DOI: 10.3390/pharmaceutics12050472
发表时间: 2020-05-01
期刊: PHARMACEUTICS
影响因子: 5.4
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