title: Chitosan nanoparticles: preparation, size evolution and stability.
abstract: OBJECTIVE
  Characterisation of chitosan-tripolyphosphate nanoparticles is presented with the aim of correlating particle shape and morphology, size distribution, surface chemistry, and production automatisation with preparation procedure, chitosan molecular weight and loaded protein.
  
  
  METHODS
  Nanoparticles were prepared by adding drop wise a tripolyphosphate-pentasodium solution to chitosan solutions under stirring. Trehalose, mannitol and polyethylene-glycol as bioprotectants were used to prevent particle aggregation and to reduce mechanical stress during freezing and drying processes.
  
  
  RESULTS
  As a novel result, time evolution of the particle size distribution curve showed the presence of a bimodal population composed of a fraction of small particles and of a second fraction of larger particles attributed to the rearrangement of particles after the addition of tripolyphosphate. Storage for 4 weeks resulted in a slight increase in average size, due to the continuous rearrangement of small particles. Improvement of nanoparticle stability after lyophilisation and spray-drying was observed in the presence of all bioprotectants. Trehalose was the best protectant for both methods. Finally, in vivo tests using chick embryos assessed the biocompatibility of chitosan, tripolyphosphate and the nanoparticles.
  
  
  CONCLUSIONS
  The simple ionotropic gelation method with low-MW chitosan was effective in achieving reproducible nanoparticles with the desired physico-chemical and safety characteristics.
authors.affiliation: Laboratory of Physical and Macromolecular Chemistry, Dept. Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rampino
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Borgogna
authors.forename: Paolo
authors.initials: P
authors.lastname: Blasi
authors.forename: Barbara
authors.initials: B
authors.lastname: Bellich
authors.forename: Attilio
authors.initials: A
authors.lastname: Cesàro
mesh_terms: D000818:Animals; D002642:Chick Embryo; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D049033:Chorioallantoic Membrane / Q000187:drug effects; D003451:Cryoprotective Agents / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D007328:Insulin / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011122:Polyphosphates / Q000008:administration & dosage / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014199:Trehalose / Q000737:chemistry
chemical_list: D003451:Cryoprotective Agents; D007328:Insulin; D011122:Polyphosphates; D012710:Serum Albumin, Bovine; D008353:Mannitol; D011092:Polyethylene Glycols; D010047:Ovalbumin; D048271:Chitosan; D014199:Trehalose; C005692:triphosphoric acid
keywords: Chitosan nanoparticles; Freeze-drying; Ionotropic gelation; Nanoparticle ageing; Protein carriers; Spray drying