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Biological Effects of Drug-Free Alginate Beads Cross-Linked by Copper Ions Prepared Using External Ionotropic Gelation

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Abstract

External ionotropic gelation offers a unique possibility to entrap multivalent ions in a polymer structure. The aim of this experimental study was to prepare new drug-free sodium alginate (ALG) particles cross-linked by Cu2+ ions and to investigate their technological parameters (particle size, sphericity, surface topology, swelling capacity, copper content, release of Cu2+ ions, mucoadhesivity) and biological activity (cytotoxicity and efficiency against the most common vaginal pathogens—Herpes simplex, Escherichia coli, Candida albicans) with respect to potential vaginal administration. Beads prepared from NaALG dispersions (3 or 4%) were cross-linked by Cu2+ ions (0.5 or 1.0 M CuCl2) using external ionotropic gelation. Prepared mucoadhesive beads with particle size over 1000 μm exhibited sufficient sphericity (all ˃0.89) and copper content (214.8–249.07 g/kg), which increased with concentration of polymer and hardening solution. Dissolution behaviour was characterized by extended burst effect, followed by 2 h of copper release. The efficiency of all samples against the most common vaginal pathogens was observed at cytotoxic Cu2+ concentrations. Anti-HSV activity was demonstrated at a Cu2+ concentration of 546 mg/L. Antibacterial activity of beads (expressed as minimum inhibition concentration, MIC) was influenced mainly by the rate of Cu2+ release which was controlled by the extent of swelling capacity. Lower MIC values were found for E. coli in comparison with C. albicans. Sample ALG-3_1.0 exhibited the fastest copper release and was proved to be the most effective against both bacteria. This could be a result of its lower polymer concentration in combination with smaller particle size and thus larger surface area.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1, 612 42, Brno, Czech Republic

    M. Pavelková, K. Kubová, J. Vysloužil, M. Kejdušová & D. Vetchý

  2. Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Palackého 1-3, 612 42, Brno, Czech Republic

    V. Celer, D. Molinková & D. Lobová

  3. Department of Biochemistry and Biophysics, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Palackého 1-3, 612 42, Brno, Czech Republic

    A. Pechová

  4. Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 267/2, 611 37, Brno, Czech Republic

    J. Vysloužil

  5. Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 296/70, 621 00, Brno, Czech Republic

    P. Kulich

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  1. M. Pavelková
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Correspondence to K. Kubová.

Additional information

This experimental work was realized by support IGA VFU Brno Czech Republic, project 306/2015/FaF.

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Pavelková, M., Kubová, K., Vysloužil, J. et al. Biological Effects of Drug-Free Alginate Beads Cross-Linked by Copper Ions Prepared Using External Ionotropic Gelation. AAPS PharmSciTech 18, 1343–1354 (2017). https://doi.org/10.1208/s12249-016-0601-4

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