Journal
PHARMACEUTICAL RESEARCH
Volume 26, Issue 8, Pages 1918-1930Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-009-9908-0
Keywords
chitosan; hyaluronic acid; macrophages; nanoparticles; toxicity
Funding
- EPSRC [EP/C543572/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/C543572/1] Funding Source: researchfish
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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. 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. 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.
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