Preparation of an alternative freeze-dried pH-sensitive cyclosporine A loaded nanoparticles formulation and its pharmacokinetic profile in rats

Pharmazie. 2009 Jan;64(1):26-31.


This work aimed to produce and develop new pH-sensitive cyclosporine A (CyA) loaded nanoparticles (CyA-NP) based on the enterically soluble copolymer Eudragit S100 and to improve the poor bioavailability of lipophilic CyA. CyA-NP and freeze-dried nanoparticles (Lac-CyA-NP, 3% lactose as cryoprotectant) were prepared using a quasi-emulsion solvent diffusion technique and freeze-drying. The encapsulation efficiency, particle size and in vitro release characteristics from the vehicle of CyA were studied individually. The bioavailability of CyA-NP and Lac-CyA-NP was evaluated in rats at a dose of 15 mg/kg as compared to Neoral. The mean particle size of CyA-NP was 44 +/- 3 nm, while the encapsulation efficiency reached 99.7%. The particle size and encapsulation efficiency of the freeze-dried formulation remained relatively stable by using 3% lactose (W/V) as a cryoprotective agent before freeze-drying and after dissolving. Significantly pH-dependent release profiles were revealed when the pH of the medium was above 6.0. The relative bioavailabilities of CyA-NP and Lac-CyA-NP were 162.1% and 130.1% compared with Neoral after oral administration at the same dosage. The results showed that the pH-sensitive CyA-loaded nanoparticles were a potential vehicle for developing a high performance CyA carrier system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Area Under Curve
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Cryoprotective Agents / chemistry
  • Cyclosporine / administration & dosage*
  • Cyclosporine / chemistry
  • Cyclosporine / pharmacokinetics*
  • Drug Compounding
  • Freeze Drying
  • Hydrogen-Ion Concentration
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / pharmacokinetics*
  • Male
  • Microscopy, Electron, Transmission
  • Nanoparticles
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley


  • Cryoprotective Agents
  • Immunosuppressive Agents
  • Cyclosporine