Porous silicon microneedle patches for delivery of polymyxin‐based antimicrobials

Nazia Tabassum, David Rudd, Li Yan, Nicolas H. Voelcker, Maria Alba
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Abstract

Abstract There is a global trend of increasing antibiotic resistance to Gram‐negative bacteria and the medical research community is looking for alternative antibiotics. Antibiotics such as polymyxin B (PMB) show excellent efficacy and low resistance rates against Gram‐negative bacteria. The topical administration of PMB, however, has clinical limitations such as minimal residence time, making it difficult for its use to treat skin infections. Here, we present porous silicon microneedle (pSi MN) patches to deliver PMB to the skin. pSi MN patches are fabricated by, first, generating the projections by dry Si etching techniques, followed by an electrochemical etching to create porous layers around the MNs. After loading PMB into the porous layer, the antibacterial activity of pSi MNs is determined by measuring the inhibition zone of Gram‐negative Escherichia coli . Next, PMB is efficiently delivered into the epidermal layer of ex vivo skin models, as confirmed by chemical mapping using matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI). The results demonstrate that pSi MN patches are an efficient and versatile tool for the transdermal delivery of PMB with maintained bioactivity and antimicrobial efficacy, thus expanding the possibilities of current transdermal drug delivery systems.
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多孔硅微针贴片用于多粘菌素类抗菌剂的递送
全球对革兰氏阴性菌的耐药性呈上升趋势,医学研究界正在寻找替代抗生素。多粘菌素B (polymyxin B, PMB)等抗生素对革兰氏阴性菌具有良好的疗效和较低的耐药率。然而,局部施用PMB有临床局限性,如最小的停留时间,使其难以用于治疗皮肤感染。在这里,我们提出了多孔硅微针(pSi MN)贴片,将PMB输送到皮肤。pSi MN贴片的制造首先通过干硅蚀刻技术产生投影,然后通过电化学蚀刻在MN周围形成多孔层。将PMB装入多孔层后,通过测量对革兰氏阴性大肠杆菌的抑制区来测定pSi MNs的抗菌活性。接下来,PMB被有效地递送到离体皮肤模型的表皮层,正如使用基质辅助激光解吸/电离质谱成像(MALDI - MSI)的化学定位所证实的那样。研究结果表明,pSi MN贴片是一种高效、通用的经皮给药工具,可保持PMB的生物活性和抗菌功效,从而扩大了目前经皮给药系统的可能性。
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