Nano spray drying: a novel method for preparing protein nanoparticles for protein therapy

Int J Pharm. 2011 Jan 17;403(1-2):192-200. doi: 10.1016/j.ijpharm.2010.10.012. Epub 2010 Oct 15.


There has been an increasing interest in the development of protein nanotherapeutics for diseases such as cancer, diabetes and asthma. Spray drying with prior micro mixing is commonly used to obtain these powders. However, the separation and collection of protein nanoparticles with conventional spray dryer setups has been known to be extremely challenging due to its typical low collection efficiency for fine particles less than 2μm. To date, there has been no feasible approach to produce these protein nanoparticles in a single step and with high yield (>70%). In this study, we explored the feasibility of the novel Nano Spray Dryer B-90 (equipped with a vibrating mesh spray technology and an electrostatic particle collector) for the production of bovine serum albumin (BSA) nanoparticles. A statistical experimental design method (Taguchi method based on three levels, five variables L(18) orthogonal array robust design) was implemented to study the effect of and optimize the experimental conditions of: (1) spray mesh size, (2) BSA solution concentration, (3) surfactant concentration, (4) drying air flow rate and (5) inlet temperature on: (1) size and (2) morphology (axial ratio). Particle size and morphology were predominantly influenced by the spray mesh size and surfactant concentration, respectively. The drying air flow rate and inlet temperature had minimal impact. Optimized production of smooth spherical nanoparticles (median size: 460±10nm, axial ratio: 1.03±0.00, span 1.03±0.03, yield: 72±4%) was achieved using the 4μm spray mesh at BSA concentration of 0.1% (w/v), surfactant concentration of 0.05% (w/v), drying flow rate of 150L/min and inlet temperature of 120°C. The Nano Spray Dryer B-90 thus offers a new, simple and alternative approach for the production of protein nanoparticles suited for a variety of drug delivery applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Carriers / chemistry*
  • Equipment Design
  • Microscopy, Electron, Scanning
  • Nanomedicine / instrumentation
  • Nanomedicine / methods*
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Particle Size
  • Proteins* / administration & dosage
  • Proteins* / chemistry
  • Proteins* / therapeutic use
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / chemistry
  • Static Electricity
  • Surface Properties
  • Technology, Pharmaceutical / instrumentation
  • Technology, Pharmaceutical / methods*


  • Drug Carriers
  • Proteins
  • Serum Albumin, Bovine