Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK.
Adv Healthc Mater. 2022 Jul;11(14):e2200036. doi: 10.1002/adhm.202200036. Epub 2022 May 11.
Antibiotic resistance is a severe global health threat and hence demands rapid action to develop novel therapies, including microscale drug delivery systems. Herein, a hierarchical microparticle system is developed to achieve bacteria-activated single- and dual-antibiotic drug delivery for preventing methicillin-resistant Staphylococcus aureus (MRSA) bacterial infections. The designed system is based on a capsosome structure, which consists of a mesoporous silica microparticle coated in alternating layers of oppositely charged polymers and antibiotic-loaded liposomes. The capsosomes are engineered and shown to release their drug payloads in the presence of MRSA toxins controlled by the Agr quorum sensing system. MRSA-activated single drug delivery of vancomycin and synergistic dual delivery of vancomycin together with an antibacterial peptide successfully kills MRSA in vitro. The capability of capsosomes to selectively deliver their cargo in the presence of bacteria, producing a bactericidal effect to protect the host organism, is confirmed in vivo using a Drosophila melanogaster MRSA infection model. Thus, the capsosomes serve as a versatile multidrug, subcompartmentalized microparticle system for preventing antibiotic-resistant bacterial infections, with potential applications to protect wounds or medical device implants from infections.
抗生素耐药性是一个严重的全球健康威胁，因此需要迅速采取行动开发新的治疗方法，包括微尺度药物输送系统。本文开发了一种分层微粒系统，以实现用于预防耐甲氧西林金黄色葡萄球菌 (MRSA) 细菌感染的细菌激活的单药和双药药物输送。该设计的系统基于一种帽状结构，由介孔二氧化硅微球涂覆在带相反电荷的聚合物和载有抗生素的脂质体交替层组成。对帽状结构进行了工程设计，使其能够在 Agr 群体感应系统控制下释放其药物有效成分，以响应 MRSA 毒素。MRSA 激活的万古霉素单药输送和万古霉素与抗菌肽的协同双药输送成功地杀死了体外的 MRSA。使用黑腹果蝇 MRSA 感染模型在体内证实了帽状结构在存在细菌的情况下选择性地输送其货物的能力，从而产生杀菌作用来保护宿主生物体。因此，帽状结构可用作一种多功能的多药物、亚区隔化的微粒系统，用于预防抗生素耐药性细菌感染，具有保护伤口或医疗器械植入物免受感染的潜在应用。
