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

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 4.7 mu m 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 macrophagederived 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 +/- 0.16 mu g/mL of rifampicin concentration in alveolar macrophages was obtained.