Formation of Protein Nano-Matrix Particles with Controlled Surface Architecture for Respiratory Drug Delivery

Abstract

To produce and examine the aerosol performance of protein nano-matrix particles with different surface roughness. Aqueous lysozyme solutions were poured into isopropanol during high-shear mixing to produce nanoparticles by precipitation. The size of the nanoparticles was varied by adjusting the precipitation conditions. The resultant suspensions were spray-dried to obtain micron-sized aggregates (nano-matrices). Smooth particles were made by spray-drying a lysozyme solution. The aggregate size distribution, surface roughness, and cohesion were evaluated. The aerosol performance was assessed by dispersing 10 mg of powder from a Rotahaler(A (R)) at 60 L/min or an AerolizerA (R) at 100 L/min into a Next Generation Impactor, followed by chemical assay (n = 3). The median volume diameter and span of the nano-matrix particles were 1.0-1.2 mu m and 1.5-1.6, respectively, which were comparable to those of the smooth particles. Surface roughness increased with the size of the primary nanoparticles. The nano-matrix particles were significantly less cohesive than the smooth particles. The fine particle fraction increased linearly with increasing surface roughness and decreasing cohesion. Nano-matrix particles with controlled surface architecture were successfully produced by spray-drying nanosuspensions. Aerosol performance was enhanced with increasing surface roughness due to the reduction in cohesion forces.