Monosized Polymeric Microspheres Designed for Passive Lung Targeting: Biodistribution and Pharmacokinetics after Intravenous Administration

Abstract

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-<i>co</i>-glycolic acid) (PLGA) MS loaded with levofloxacin using a flow-focusing glass microfluidic chip. <i>In vitro</i> characterization showed that the encapsulated LVX displayed a biphasic controlled release during 5 days and preserved its antibacterial activity. The MS degradation was investigated <i>in vitro</i> by cross-sectioning the MS using a focused ion beam scanning electron microscope and <i>in vivo</i> 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 <i>in vivo</i> was 3 times faster than that <i>in vitro</i>. 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 ¹¹¹indium-labeled PLGA MS was performed <i>in vivo</i> 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.