Formation of protein nano-matrix particles with controlled surface architecture for respiratory drug delivery

Pharm Res. 2011 Apr;28(4):788-96. doi: 10.1007/s11095-010-0332-2. Epub 2010 Dec 7.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Propanol / chemistry
  • Administration, Inhalation
  • Aerosols
  • Chemistry, Pharmaceutical
  • Drug Carriers / chemistry*
  • Dry Powder Inhalers
  • Light
  • Microscopy, Atomic Force
  • Microscopy, Electron, Scanning
  • Muramidase / chemistry*
  • Nanoparticles / chemistry*
  • Particle Size
  • Pharmaceutical Preparations / administration & dosage*
  • Scattering, Radiation
  • Surface Properties

Substances

  • Aerosols
  • Drug Carriers
  • Pharmaceutical Preparations
  • Muramidase
  • 2-Propanol