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

Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals

“…Observed yields in the range of ~ 75-80% are plausible, since the complete collection is impossible due to technical reasons red in case of the organic NCs to determine the NP distribution within the MPs. FIB-SEM: Samples were analyzed as previously described [29], with slight modifications. Briefly, powders were dispersed in ethyl acetate and dried on a 5-mm × 5-mm silicon wafer under ambient conditions before the samples were glued on Al stubs using silver paste.…”

Pulmonary Targeting Crosslinked Cyclodextrin Metal–Organic Frameworks for Lung Cancer Therapy

“…[ 19 ] For example, previous studies have reported that particles slightly larger than the capillary diameter are more easily entrapped in alveolar capillaries, thereby efficiently reaching lung targets. [ 20 ] Moreover, the zeta potential of nanocarriers affects their pharmacokinetic processes and biodistribution in the body. For instance, surface modification of nanoplatforms, especially in surface charge, is a common way to avoid opsonization.…”

Lung Targeted Lipopolymeric Microspheres of Dexamethasone for the Treatment of ARDS

“…It generates vitamin E in vivo, which also participates in lung surfactant biosynthesis. PLGA microspheres have been proved suitable for passive lung targeting and pulmonary therapy [44][45][46] Polydispersity index was found to be 0.31 indicating narrow size distribution. The same is also revealed from the SEM and TEM images (Figure 1B,C) showing multiple microspheres of uniform size that were round in shape with smooth surface and absence of particle aggregation.…”

“…It generates vitamin E in vivo, which also participates in lung surfactant biosynthesis. PLGA microspheres have been proved suitable for passive lung targeting and pulmonary therapy [ 44 , 45 , 46 ].…”