Effects of l-leucine on PLGA microparticles for pulmonary administration prepared using spray drying: Fine particle fraction and phagocytotic ratio of alveolar macrophages

Abstract

Recently, non-spherical particles for inhalation have attracted attention. In the previous study, we reported non-spherical nanocomposite particles suitable for transpulmonary administration using amino acids [I. Takeuchi et. al., Colloids Surf. A 529 (2017) 387–393]. In this study, to apply this nanocomposite particle preparation method using amino acid to microparticles for inhalation, the influence of l-leucine on small fine particle fraction (FPF) values of poly(lactic-co-glycolide) (PLGA) microparticles and their phagocytotic ratio of alveolar macrophages was investigated. We prepared non-spherical rifampicin-loaded PLGA microparticles for inhalation using l-leucine and l-aspartic acid. The amino acids were added in aqueous phase, and the microparticles were prepared using a spray dryer via emulsion. Spherical rifampicin-loaded PLGA microparticles were also prepared using a conventional spray drying method for comparison. The FPF below 4.7μm of microparticles prepared using an aqueous phase with a leucine concentration of 0.2% (w/v) increased to 6.9 times (43.4±5.7%) that of conventional microspheres (6.3±4.0%). From the measurement result of the tap density, it was found that the shape of the particle had a large effect on the FPF value in this study. To evaluate the effectiveness of this particle in treating tuberculosis, microparticles phagocytotic ratio of alveolar macrophages (rat alveolar macrophage-derived NR8383 cells) was studied. The phagocytotic ratio of the microparticles prepared using an aqueous phase with a leucine concentration of 0.2% (w/v) was significantly higher than the spherical microparticles, and 0.34±0.16μg/mL of rifampicin concentration in alveolar macrophages was obtained.