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Optimisation of the self-assembly process: production of stable, alginate-based polyelectrolyte nanocomplexes with protamine

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Abstract

The aim of this work was to investigate the possibility of covalent cross-linker-free, polyelectrolyte complex formation at the nanoscale between alginic acid (as sodium alginate, ALG) and protamine (PROT). Optimisation of the self-assembly conditions was performed by varying the type of polymer used, pH of component solutions, mass mixing ratio of the components and the speed and order of component addition on the properties of complexes. Homogenous particles with nanometric sizes resulted when an aqueous dispersion of ALG was rapidly mixed with a solution of PROT. The polyelectrolyte complex between ALG and PROT was confirmed by infrared spectroscopy. To facilitate incorporation of drugs soluble at low pH, pH of ALG dispersion was decreased to 2; however, no nanoparticles (NPs) were formed upon complexation with PROT. Adjusting pH of PROT solution to 3 resulted in the formation of cationic or anionic NPs with a size range 70–300 nm. Colloidal stability of selected alginic acid low/PROT formulations was determined upon storage at room temperature and in liquid media at various pH. Physical stability of NPs correlated with the initial surface charge of particles and was time- and pH-dependent. Generally, better stability was observed for anionic NPs stored as native dispersions and in liquids covering a range of pH.

Schematic presenting the formation and size of alginate/protamine nanoparticles

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Authors and Affiliations

  1. School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland

    Maria Dul, Krzysztof J. Paluch, Anne Marie Healy, Astrid Sasse & Lidia Tajber

  2. Bradford School of Pharmacy, School of Life Sciences, Centre for Pharmaceutical Engineering Science, University of Bradford, Norcroft Building, Richmond Road, Bradford W. Yorks, BD7 1DP, UK

    Krzysztof J. Paluch

Authors
  1. Maria Dul
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  2. Krzysztof J. Paluch
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  3. Anne Marie Healy
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  4. Astrid Sasse
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  5. Lidia Tajber
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Correspondence to Lidia Tajber.

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Funding

This study was funded by Merrion Pharmaceuticals Ireland. This work was also supported by the Synthesis and Solid State Pharmaceutical Centre funded by the Science Foundation Ireland under grant number 12/RC/2275.

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The authors declare that they have no conflict of interest.

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Dul, M., Paluch, K.J., Healy, A.M. et al. Optimisation of the self-assembly process: production of stable, alginate-based polyelectrolyte nanocomplexes with protamine. J Nanopart Res 19, 221 (2017). https://doi.org/10.1007/s11051-017-3901-z

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  • DOI: https://doi.org/10.1007/s11051-017-3901-z

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