Assessment of Antimicrobic, Antivirotic and Cytotoxic Potential of Alginate Beads Cross-Linked by Bivalent Ions for Vaginal Administration

Abstract

Antimicrobial agent abuse poses a serious threat for future pharmacotherapy, including vaginal administration. The solution can be found in simple polymeric systems with inherent antimicrobial properties without the need to incorporate drugs, for instance alginate beads cross-linked by bivalent ions. The main goal of the presented study was to provide improvement on the well-documented cytotoxicity of Cu2+ cross-linked alginate. Alginate beads were prepared by external ionotropic gelation by cross-linking with Cu2+, Ca2+ and Zn2+ ions, separately and in mixtures. Morphological properties, swelling capacity, ion release and efficacy against the most common vaginal pathogens (C. albicans, E. coli, E. faecalis and virus strain—human herpesvirus type 1) were evaluated. The prepared particles (particle size 1455.68 ± 18.71–1756.31 ± 16.58 µm) had very good sphericity (0.86 ± 0.04–0.97 ± 0.06). In mixture samples, Cu2+ hampered second ion loading, and was also released incompletely (18.75–44.8%) compared to the single ion Cu2+ sample (71.4%). Efficacy against the selected pathogens was confirmed in almost all samples. Although anticipating otherwise, ion mixture samples did not show betterment over a Cu2+ cross-linked sample in cytotoxicity–pathogen efficacy relation. However, the desired improvement was found in a single ion Zn2+ sample whose minimal inhibition concentrations against the pathogens (0.6–6.12 mM) were close to, or in the same mathematical order as, its toxic concentration of 50 (1.891 mM). In summary, these findings combined with alginate’s biocompatibility and biodegradability give the combination solid potential in antimicrobial use.

Comparison of green bio-based cerium/alginate vs. copper/alginate beads: a study of vibrational and thermal properties using experimental and theoretical methods

“…It is also observed that these beads are clearly folded and cracked. As reported, these cracks were detected in the case of alginate beads cross-linked with divalent cations such as copper and calcium [70], in agreement with our results. On the other hand, the Alg@Ce bead is morphologically different., Firstly, beads are not cracked (Fig.…”

In‐situ Synthesis of Highly Potent Antibacterial Copper‐Based MOFs/Sodium Alginate Composite Beads

“…This improvement is primarily attributed to the in-situ formation of copper-based MOFs within the copper-ion-crosslinked alginate beads, resulting in a three-dimensional structural arrangement. [39][40][41]…”

“…This observed efficacy is primarily attributed to copper ions interacting with the bacterial membranes, leading to the release of cellular contents and consequent cell death. [39,40] Copper ions can affect gram-positive and gram-negative bacteria differently owing to differences in their cell wall structures and membrane characteristics. Gram-positive bacteria feature a cell membrane consisting of a singular thick peptidoglycan layer.…”

“…In contrast, gram-negative bacteria have an extra outer peptidoglycan layer, which makes it slightly challenging for copper ions to initiate their antibacterial effects in comparison with gram-positive bacteria. [39,40] The antibacterial performance of the CuMOF-Tart/Alg and CuMOF-Oxa/Alg composite beads was notably more potent, displaying an average inhibition zone exceeding 23 mm against both gram-positive (Staphylococcus aureus and Bacillus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) microorganisms. This enhanced efficacy is a result of the synergistic effect arising from the coordination of copper ions and oxalic acid or tartaric acid ligands, which are known for their antibacterial efficiency, forming MOFs within the alginate matrix.…”

Regulation of Staphylococcus aureus Virulence and Application of Nanotherapeutics to Eradicate S. aureus Infection

“…Alginate/chitosan NPs were tested with rifampicin encapsulation against MSSA and MRSA in pulmonary intracellular infections [ 243 ]. The results revealed that the alginate NPs have great potential as novel antimicrobial nanomaterials [ 242 , 244 ].…”