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Chitosan/TPP and Chitosan/TPP-hyaluronic Acid Nanoparticles: Systematic Optimisation of the Preparative Process and Preliminary Biological Evaluation

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Abstract

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.

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Acknowledgments

The authors want to thank Dr. Philip Day (School of Translational Medicine, University of Manchester) for the helpful discussions. Financial support from EPSRC (grant No. EP/C543564/1 and Advanced Research Fellowship for NT) and from the University of Naples Federico II is gratefully acknowledged.

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Authors and Affiliations

  1. School of Pharmacy, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK

    Alessandro Nasti, Noha M. Zaki, Piero de Leonardis, Suwipa Ungphaiboon, Proramate Sansongsak & Nicola Tirelli

  2. Department of Pharmaceutical Chemistry and Toxicology, University of Naples “Federico II”, Via D. Montesano 49, 80131, Napoli, Italy

    Alessandro Nasti & Maria Grazia Rimoli

  3. Department of Pharmaceutics, Faculty of Pharmacy, Ain Shams University, Monazamet El Wehda El Afrikia St., El Abbassia, Cairo, Egypt

    Noha M. Zaki

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  1. Alessandro Nasti
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Correspondence to Nicola Tirelli.

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Alessandro Nasti and Noha M. Zaki have equally contributed to this manuscript.

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Nasti, A., Zaki, N.M., de Leonardis, P. et al. Chitosan/TPP and Chitosan/TPP-hyaluronic Acid Nanoparticles: Systematic Optimisation of the Preparative Process and Preliminary Biological Evaluation. Pharm Res 26, 1918–1930 (2009). https://doi.org/10.1007/s11095-009-9908-0

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