Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China.
School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore, 637459, Singapore.
Adv Sci (Weinh). 2021 Nov;8(21):e2102327. doi: 10.1002/advs.202102327. Epub 2021 Sep 8.
The development of potent antibiotic alternatives with rapid bactericidal properties is of great importance in addressing the current antibiotic crisis. One representative example is the topical delivery of predatory bacteria to treat ocular bacterial infections. However, there is a lack of suitable methods for the delivery of predatory bacteria into ocular tissue. This work introduces cryomicroneedles (cryoMN) for the ocular delivery of predatory Bdellovibrio bacteriovorus (B. bacteriovorus) bacteria. The cryoMN patches are prepared by freezing B. bacteriovorus containing a cryoprotectant medium in a microneedle template. The viability of B. bacteriovorus in cryoMNs remains above 80% as found in long-term storage studies, and they successfully impede the growth of gram-negative bacteria in vitro or in a rodent eye infection model. The infection is significantly relieved by nearly six times through 2.5 days of treatment without substantial effects on the cornea thickness and morphology. This approach represents the safe and efficient delivery of new class of antimicrobial armamentarium to otherwise impermeable ocular surface and opens up new avenues for the treatment of ocular surface disorders.
开发具有快速杀菌特性的强效抗生素替代品对于应对当前的抗生素危机至关重要。一个代表性的例子是局部递送捕食性细菌来治疗眼部细菌感染。然而，缺乏将捕食性细菌递送到眼部组织的合适方法。本工作介绍了用于眼部递送捕食性蛭弧菌（Bdellovibrio bacteriovorus，B. bacteriovorus）的 cryomicroneedles（cryoMN）。cryoMN 贴片是通过将含有冷冻保护剂介质的 B. bacteriovorus 在微针模板中冷冻制备的。在长期储存研究中，cryoMN 中 B. bacteriovorus 的存活率保持在 80%以上，并且它们成功地抑制了体外或啮齿动物眼部感染模型中的革兰氏阴性菌的生长。通过 2.5 天的治疗，感染显著缓解了近六倍，而对角膜厚度和形态没有明显影响。这种方法代表了将新型抗菌武器安全有效地递送到原本不可渗透的眼部表面，并为治疗眼部表面疾病开辟了新途径。
