Effects of lower alcohols on nanocomposite particles for inhalation prepared using O/W emulsion.

BACKGROUND: Inhalable nanocomposite particles using O/W emulsions were studied. The effect of the composition of the dispersed phase on the nanoparticles in the nanocomposite particles was reported, however, the effect on the inhalation characteristics of nanocomposite particles has not been investigated. OBJECTIVE: The aim of this study was to study the effects of lower alcohols in the dispersed phase of O/W emulsions on inhalable nanocomposite particles. METHODS: Nanocomposite particles were prepared using a spray dryer from O/W emulsion. A mixed solution of dichloromethane and lower alcohols in which rifampicin (RFP) and poly(L-lactide-co-glycolide) were dissolved was used as a dispersed phase, and an aqueous solution in which arginine and leucine were dissolved was used as a continuous phase. RESULTS: We succeeded in preparing non-spherical nanocomposite particles with an average diameter of 9.01-10.91 µm. The results of the fine particle fraction (FPF) measurement showed that the higher the hydrophobicity of the lower alcohol mixed in the dispersed phase, the higher the FPF value. The FPF value of the nanocomposite particles was significantly increased by using ethanol and 1-propanol. CONCLUSIONS: The results were revealed that mixing 1-propanol with the dispersed phase increased the amount of RFP delivered to the lungs.

Effect of the Conformation of Poly(L-lactide-co-glycolide) Molecules in Organic Solvents on Nanoparticle Size.

Controlling the size of nanoparticles is important for drug delivery methods such as pulmonary administration, transdermal administration, and intravenous administration. In this study, we have investigated the effect of polymer conformation in organic solvents on the size of the nanoparticles. Poly(L-lactide-co-glycolide) (PLLGA), a promising nanoparticle carrier, was used as the polymer. A mixed solution of dichloromethane, which is a good solvent, and a lower alcohol (methanol, ethanol, and 1-propanol), which is a poor solvent, was used as the solvent for dissolving PLLGA. An oil-in-water emulsion was prepared by sonication using the mixed solution of organic solvents in which PLLGA was dissolved as a dispersed phase and an amino acid aqueous solution as a continuous phase. Nanocomposite particles were prepared from the emulsion using a spray dryer and redispersed in purified water to obtain the PLLGA nanoparticles. The conformation of PLLGA molecules in the organic solvents was evaluated by analyzing the results of the viscosity measurements. The polymer coil radius and the volume per polymer coil were observed to decrease with the increase in the ratio of the lower alcohol in the solvent, whereas these values tended to decrease with the use of more hydrophilic lower alcohols. In addition, based on the results of the calculated entanglement index, it was found that when the hydrophobicity of the dispersed phase is reduced, the polymers were hardly entangled with each other. These results were significant, specifically when the ratio of the lower alcohol in the solvent was low. Estimation of the Pearson's correlation coefficients indicated that there were positive correlations between these indices and the mean volume diameter of PLLGA nanoparticles. This study shows that changing the composition of the dispersed phase, in which the PLLGA is dissolved, can change the conformation of the PLLGA molecules and control the size of the PLLGA nanoparticles.