Formation of protein nano-matrix particles with controlled surface architecture for respiratory drug delivery.
OBJECTIVE
To produce and examine the aerosol performance of protein nano-matrix particles with different surface roughness.


METHODS
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(®) at 60 L/min or an Aerolizer® at 100 L/min into a Next Generation Impactor, followed by chemical assay (n=3).


RESULTS
The median volume diameter and span of the nano-matrix particles were 1.0-1.2 μm 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.


CONCLUSIONS
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.
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Building A15, Camperdown, NSW, 2006, Australia.
Philip Chi Lip
PC
Kwok
Amolnat
A
Tunsirikongkon
William
W
Glover
Hak-Kim
HK
Chan
D019840:2-Propanol / Q000737:chemistry; D000280:Administration, Inhalation; D000336:Aerosols; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D058995:Dry Powder Inhalers; D008027:Light; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012542:Scattering, Radiation; D013499:Surface Properties
D000336:Aerosols; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D009113:Muramidase; D019840:2-Propanol