Agnoletti Monica, Rodríguez-Rodríguez Cristina, Kłodzińska Sylvia N, Esposito Tullio V F, Saatchi Katayoun, Mørck Nielsen Hanne, Häfeli Urs O
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2100, Denmark.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
ACS Nano. 2020 Jun 23;14(6):6693-6706. doi: 10.1021/acsnano.9b09773. Epub 2020 May 27.
Local as well as systemic therapy is often used to treat bacterial lung infections. Delivery of antibiotics to the vascular side of infected lung tissue using lung-targeting microspheres (MS) is a good alternative to conventional administration routes, allowing for localized high levels of antibiotics. This delivery route can also complement inhaled antibiotic therapy, especially in the case of compromised lung function. We prepared and characterized monodisperse poly(lactic--glycolic acid) (PLGA) MS loaded with levofloxacin using a flow-focusing glass microfluidic chip. characterization showed that the encapsulated LVX displayed a biphasic controlled release during 5 days and preserved its antibacterial activity. The MS degradation was investigated by cross-sectioning the MS using a focused ion beam scanning electron microscope and by histological examination of lung tissue from mice intravenously administered with the MS. The MS showed changes in the surface morphology and internal matrix, whereas the degradation was 3 times faster than that . No effect on the viability of endothelial and lung epithelial cells or hemolytic activity was observed. To evaluate the pharmacokinetics and biodistribution of the MS, complete quantitative imaging of the indium-labeled PLGA MS was performed with single-photon emission computed tomography imaging over 10 days. The PLGA MS distributed homogeneously in the lung capillaries. Overall, intravenous administration of 12 μm PLGA MS is suitable for passive lung targeting and pulmonary therapy.
局部和全身治疗通常用于治疗细菌性肺部感染。使用肺部靶向微球（MS）将抗生素递送至受感染肺组织的血管侧是传统给药途径的良好替代方案，可实现局部高浓度的抗生素。这种给药途径还可以补充吸入性抗生素治疗，特别是在肺功能受损的情况下。我们使用流动聚焦玻璃微流控芯片制备并表征了负载左氧氟沙星的单分散聚乳酸-乙醇酸共聚物（PLGA）微球。表征显示，包封的左氧氟沙星在5天内呈现双相控释，并保留其抗菌活性。通过使用聚焦离子束扫描电子显微镜对微球进行横截面分析以及对静脉注射微球的小鼠肺组织进行组织学检查来研究微球的降解情况。微球的表面形态和内部基质发生了变化，但其降解速度比[对比物]快3倍。未观察到对内皮细胞和肺上皮细胞活力或溶血活性的影响。为了评估微球的药代动力学和生物分布，在10天内使用单光子发射计算机断层扫描成像对铟标记的PLGA微球进行了完整的定量成像。PLGA微球在肺毛细血管中均匀分布。总体而言，静脉注射12μm的PLGA微球适用于被动肺部靶向和肺部治疗。
