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使用由透明质酸钠制成的新型自溶性微针阵列改善大鼠琥珀酸舒马曲坦的透皮给药

Improvement of transdermal delivery of sumatriptan succinate using a novel self-dissolving microneedle array fabricated from sodium hyaluronate in rats.

作者信息

Wu Dan, Quan Ying-shu, Kamiyama Fumio, Kusamori Kosuke, Katsumi Hidemasa, Sakane Toshiyasu, Yamamoto Akira

机构信息

Department of Biopharmaceutics, Kyoto Pharmaceutical University.

出版信息

Biol Pharm Bull. 2015;38(3):365-73. doi: 10.1248/bpb.b14-00502.

Abstract

The purpose of the present study was to develop an alternative transdermal formulation containing sumatriptan succinate (SS) for the treatment of migraine. Novel self-dissolving SS-loaded microneedle arrays (MNs) were fabricated from sodium hyaluronate and their efficacy for transdermal delivery of SS was characterized. The resulting MNs maintained their skin piercing abilities for at least 30 min after being placed at a high relative humidity of 75%. Rapid release of SS from the MNs was also observed in vitro. Optical coherence tomography images demonstrated that MNs were able to successfully pierce into rat skin without any bending or cracking, and needles were completely dissolved within 1 h. MNs significantly increased transepidermal water loss; however, skin barrier function gradually recovered to control levels within 24 h, in contrast to the skin damage observed after tape stripping treatment. These findings indicated that the micropores created by MNs quickly resealed, and that the skin damage was reversible. Furthermore, a dose-dependent plasma concentration of SS was obtained after transdermal delivery using SS-loaded MNs in rats. Absorption of SS delivered by MNs was similar to that observed after subcutaneous injection and was associated with high bioavailability (ca. 90%), which was much higher than that produced by oral administration. These findings suggested that application of SS-loaded MNs to the skin provided an effective alternative approach to enhance the transdermal delivery of SS without serious skin damage, and would be likely to improve patient compliance.

摘要

本研究的目的是开发一种含有琥珀酸舒马曲坦(SS)的新型透皮制剂用于治疗偏头痛。由透明质酸钠制备了新型载有SS的自溶性微针阵列(MNs),并对其透皮递送SS的效果进行了表征。所得MNs在相对湿度75%的高湿度环境下放置至少30分钟后仍保持其皮肤穿刺能力。体外实验还观察到SS从MNs中快速释放。光学相干断层扫描图像显示MNs能够成功刺入大鼠皮肤,无任何弯曲或破裂,且针在1小时内完全溶解。MNs显著增加了经表皮水分流失;然而,与胶带剥离处理后观察到的皮肤损伤不同,皮肤屏障功能在24小时内逐渐恢复到对照水平。这些发现表明MNs造成的微孔能迅速重新封闭,且皮肤损伤是可逆的。此外,在大鼠中使用载有SS的MNs进行透皮递送后,获得了剂量依赖性的SS血浆浓度。MNs递送的SS的吸收与皮下注射后观察到的相似,且具有高生物利用度(约90%),远高于口服给药产生的生物利用度。这些发现表明,将载有SS的MNs应用于皮肤提供了一种有效的替代方法,可增强SS的透皮递送且不会造成严重的皮肤损伤,并且可能会提高患者的依从性。

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