Center for Biopharmaceuticals and Biobarriers in Drug Delivery, Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark.
Drug Deliv Transl Res. 2021 Aug;11(4):1634-1654. doi: 10.1007/s13346-021-00954-1. Epub 2021 Mar 10.
Recalcitrant respiratory tract infections caused by bacteria have emerged as one of the greatest health challenges worldwide. Aerosolized antimicrobial therapy is becoming increasingly attractive to combat such infections, as it allows targeted delivery of high drug concentrations to the infected organ while limiting systemic exposure. However, successful aerosolized antimicrobial therapy is still challenged by the diverse biological barriers in infected lungs. Nanoparticle-mediated pulmonary drug delivery is gaining increasing attention as a means to overcome the biological barriers and accomplish site-specific drug delivery by controlling release of the loaded drug(s) at the target site. With the aim to summarize emerging efforts in combating respiratory tract infections by using nanoparticle-mediated pulmonary delivery strategies, this review provides a brief introduction to the bacterial infection-related pulmonary diseases and the biological barriers for effective treatment of recalcitrant respiratory tract infections. This is followed by a summary of recent advances in design of inhalable nanoparticle-based drug delivery systems that overcome the biological barriers and increase drug bioavailability. Finally, challenges for the translation from exploratory laboratory research to clinical application are also discussed and potential solutions proposed.
耐药性呼吸道感染已成为全球面临的最大健康挑战之一。雾化抗菌治疗因其可将高浓度药物靶向递送至感染器官,同时限制全身暴露,因此越来越受到关注。然而,成功的雾化抗菌治疗仍然受到感染肺部中多种生物屏障的挑战。纳米颗粒介导的肺部药物递送作为一种克服生物屏障并通过控制靶向部位加载药物的释放来实现靶向药物递送的手段,受到越来越多的关注。本综述旨在总结使用纳米颗粒介导的肺部递药策略来对抗呼吸道感染的最新进展,首先简要介绍与细菌感染相关的肺部疾病和有效治疗耐药性呼吸道感染的生物屏障,然后总结克服生物屏障并提高药物生物利用度的吸入型纳米颗粒给药系统的最新设计进展。最后,还讨论了从探索性实验室研究到临床应用转化的挑战,并提出了潜在的解决方案。