Many chronic wounds exhibit high matrix metalloproteinase (MMP) activity that impedes the normal wound healing process. Intradermal delivery (IDD) of sub-antimicrobial concentrations of doxycycline, as an MMP inhibitor, could target early stages of chronic wound development and inhibit further wound progression. To deliver doxycycline intradermally, the skin barrier must be disrupted. Microneedle rollers offer a minimally invasive technique to penetrate the skin by creating multiple microchannels that act as temporary conduits for drugs to diffuse through. In this study, an innovative and facile approach for delivery of doxycycline across Strat-MTM membrane was investigated using microneedle rollers. The quantity and rate of doxycycline diffusing through the micropores directly correlated with increasing microneedle lengths (250, 500 and 750 μm). Treatment of Strat-MTM with microneedle rollers resulted in a reduction in fibroblast-mediated collagen gel contraction and MMP activity compared with untreated Strat-MTM. Our results show that treatment of an epidermal mimetic with microneedle rollers provides sufficient permeabilization for doxycycline diffusion and inhibition of MMP activity. We conclude that microneedle rollers are a promising, clinically ready tool suitable for delivery of doxycycline intradermally to treat chronic wounds.

译文

:许多慢性伤口均表现出高基质金属蛋白酶(MMP)活性,阻碍了正常伤口的愈合过程。皮下递送(IDD)的多西环素抗微生物剂浓度(作为MMP抑制剂)可以靶向慢性伤口发展的早期阶段,并抑制伤口的进一步发展。为了在皮肤内递送强力霉素,必须破坏皮肤屏障。微针辊通过创建多个微通道作为药物扩散的临时导管,从而提供了一种微创技术来穿透皮肤。在这项研究中,使用微针辊研究了一种新颖而简便的方法,用于在多股Strat-MTM膜上递送强力霉素。多西环素扩散通过微孔的数量和速率与微针长度(250、500和750μm)的增加直接相关。与未处理的Strat-MTM相比,用微针滚轮治疗Strat-MTM减少了成纤维细胞介导的胶原凝胶收缩和MMP活性。我们的结果表明,用微针辊治疗表皮模拟物为多西环素扩散和抑制MMP活性提供了足够的通透性。我们得出的结论是,微针滚轮是一种有前途的,临床上可立即使用的工具,适合皮内输送强力霉素治疗慢性伤口。

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