Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin
Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin
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DOI：
10.1016/j.ejpb.2013.10.001
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发表时间：
2014-02-01
影响因子：
4.9
通讯作者：
Yamamoto, Akira
中科院分区：
文献类型：
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作者：
Liu, Shu;Jin, Mei-na;Yamamoto, Akira
本研究的目的是开发以透明质酸（HA）为材料制造的新型可溶性微针阵列，并提高相对高分子量药物的透皮渗透性。本研究采用平均分子量为4 kDa的异硫氰酸荧光素标记的右旋糖酐（FD4）作为相对较高分子量的模型药物。微针阵列显着增加了经表皮水分流失（TEWL）并降低了经皮电阻（TER），表明它们可以刺穿皮肤并成功创建药物渗透途径。在微针阵列组中，TEWL 和 TER 几乎恢复到基线水平，并且与胶带剥离治疗产生的通路相比，微针产生的相对较小的通路迅速恢复。这些发现证实微针阵列非常安全。此外，我们发现使用微针阵列的FD4的透皮渗透性比FD4溶液的透皮渗透性高得多。此外，我们发现微针阵列对于增加皮肤中积累的 FD4 量更有效。这些发现表明，使用由HA制成的新型微针阵列是一种非常有用且有效的策略，可以改善药物的透皮递送，特别是相对高分子量的药物，而不会严重损害皮肤。 (c) 2013 Elsevier B.V. 保留所有权利。
The purpose of this study was to develop novel dissolving microneedle arrays fabricated from hyaluronic acid (HA) as a material and to improve the transdermal permeability of relatively high molecular weight drugs. In this study, fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4 kDa (FD4) was used as a model drug with a relatively high molecular weight. The microneedle arrays significantly increased transepidermal water loss (TEWL) and reduced transcutaneous electrical resistance (TER), indicating that they could puncture the skin and create drug permeation pathways successfully. Both TEWL and TER almost recovered to baseline levels in the microneedle array group, and relatively small pathways created by the microneedles rapidly recovered as compared with those created by a tape stripping treatment. These findings confirmed that the microneedle arrays were quite safe. Furthermore, we found that the transdermal permeability of FD4 using the microneedle arrays was much higher than that of the FD4 solution. Furthermore, we found that the microneedle arrays were much more effective for increasing the amount of FD4 accumulated in the skin. These findings indicated that using novel microneedle arrays fabricated from HA is a very useful and effective strategy to improve the transdermal delivery of drugs, especially relatively high molecular weight drugs without seriously damaging the skin. (c) 2013 Elsevier B.V. All rights reserved.