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Abstract：
Pulmonary infections complicate chronic lung diseases requiring attention to both the pathophysiology and complexity associated with infection management. Patients with cystic fibrosis (CF) struggle with continuous bouts of pulmonary infections, contributing to lung destruction and eventual mortality. Additionally, CF patients struggle with airways that are highly viscous, with accumulated mucus creating optimal environments for bacteria colonization. The unique physiology and altered airway environment provide an ideal niche for bacteria to change their phenotype often becoming resistant to current treatments. Colonization with multiple pathogens at the same time further complicate treatment algorithms, requiring drug combinations that can challenge CF patient tolerance to treatment. The goal of this research initiative was to explore the utilization of a microparticle antibiotic delivery system, which could provide localized and sustained antibiotic dosing. The outcome of this work demonstrates the feasibility of providing efficient localized delivery of antibiotics to manage infection using both preclinical in vitro and in vivo CF infection models. The studies outlined in this manuscript demonstrate the proof-of-concept and unique capacity of polymerized cyclodextrin microparticles to provide site-directed management of pulmonary infections.
摘要：
肺部感染使慢性肺部疾病复杂化，需要注意与感染管理相关的病理生理学和复杂性。囊性纤维化（CF）患者与持续的肺部感染搏斗，导致肺破坏和最终死亡。此外,CF患者与高度粘稠的气道斗争，积聚的粘液为细菌定植创造了最佳环境。独特的生理学和改变的气道环境为细菌提供了理想的生态位，以改变其表型，通常对当前的治疗产生抗性。同时有多种病原体的定植进一步使治疗算法复杂化，需要可以挑战CF患者对治疗耐受性的药物组合。这项研究计划的目标是探索微粒抗生素递送系统的利用，这可以提供局部和持续的抗生素给药。这项工作的结果证明了使用临床前体外和体内CF感染模型提供抗生素的有效局部递送以管理感染的可行性。本手稿中概述的研究证明了聚合环糊精微粒的概念验证和独特能力，可提供肺部感染的定点管理。
