Chitosan/TPP and chitosan/TPP-hyaluronic acid nanoparticles: systematic optimisation of the preparative process and preliminary biological evaluation

Pharm Res. 2009 Aug;26(8):1918-30. doi: 10.1007/s11095-009-9908-0. Epub 2009 Jun 9.


Purpose: Chitosan is one of the most sought-after components for designing nanoparticles for drug delivery applications. However, despite the large number of studies, reproducibility is often an issue; generally more attention should be focused on purity and precise characterization of the starting material, as well as on the development of robust preparative procedures.

Methods: Using a rational experimental design, we have studied the influence of a number of orthogonal factors (pH, concentrations, ratios of components, different methods of mixing) in the preparation of chitosan/triphosphate (TPP) nanoparticles and in their coating with hyaluronic acid (HA), aiming at the minimisation of size polydispersity, the maximisation of zeta potential and long-term stability, and at the control over average nanoparticle size.

Results and conclusion: Three optimised nanoparticles have been developed (two uncoated and one HA-coated) and their toxicity on fibroblasts and macrophages has been evaluated: experiments showed the beneficial character of HA-coating in the reduction of toxicity (IC50 raised from 0.7-0.8 mg/mL to 1.8 mg/mL) and suggested that the uncoated chitosan/TPP nanoparticles had toxic effects following internalisation rather than membrane disruption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chitosan / chemistry*
  • Chitosan / isolation & purification
  • Drug Evaluation, Preclinical
  • Hyaluronic Acid / chemistry*
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Mice
  • Nanoparticles*


  • Hyaluronic Acid
  • Chitosan