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


CONCLUSIONS
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.
Nasti
Alessandro
A
School of Pharmacy, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK.
Zaki
Noha M
NM
de Leonardis
Piero
P
Ungphaiboon
Suwipa
S
Sansongsak
Proramate
P
Rimoli
Maria Grazia
MG
Tirelli
Nicola
N
D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry* / Q000302:isolation & purification; D004353:Drug Evaluation, Preclinical; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D053758:Nanoparticles
D006820:Hyaluronic Acid; D048271:Chitosan