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  • N.V. Dubashynskaya
  • S.G. Zhuravskii
  • A.Y. Borovskoy
  • A.N. Bokatyi
  • T.S. Sall
  • T.S. Egorova
  • E.V. Demyanova
  • E.A. Murashko
  • D.V. Mukhametdinova
  • A.Y. Shasherina
  • Y.A. Anufrikov
  • Y.A. Skorik
This study investigates the development of innovative polyelectrolyte complexes (PECs) based on polysaccharides, carrageenan (CRG) and cyanocobalamin-chitosan (CSB12), for the enhanced delivery of colistin (CT), a last-resort antibiotic used to treat multidrug-resistant Gram-negative bacterial infections. Two novel systems were engineered: CRG-CT and CRG-CT-CSB12 PECs. The CRG-CT PECs displayed a hydrodynamic diameter of 220 nm and a ζ-potential of −35.6 mV, whereas the CRG-CT-CSB12 PECs were smaller (140 nm) and exhibited a positive charge (ζ-potential of +30.1 mV). For CRG, the binding constants for CT interactions were reported for the first time, demonstrating a twofold increase in strength compared to those of hyaluronic acid. This enhanced binding affinity correlates with prolonged drug release and a more pronounced reduction in nephro- and neurotoxicity relative to previously established systems. Both systems demonstrated sustained release of CT, with only 23 % of the drug released over 24 h, and a two fold reduction in the minimum inhibitory concentration against Pseudomonas aeruginosa compared to free CT. Notably, the PECs showed no nephro- or neurotoxicity in human cell line models (HEK 293 and T-98G). The CRG-CT-CSB12 PECs also exhibited superior intestinal permeability (Papp = 7.4 × 10−6 cm/s) in Caco-2 cell monolayers, indicating their suitability for oral administration. In vivo studies in a rodent model confirmed the stability of CRG-CT PECs in the bloodstream and their lack of acute toxicity at therapeutic doses. These findings highlight the potential of CRG-CT and CRG-CT-CSB12 PECs as effective, and innovative nanoantibiotics for combating multidrug-resistant infections, with particular promise for oral delivery. © 2025 Elsevier B.V., All rights reserved.
Original languageEnglish
Article number137788
JournalColloids Surf. A Physicochem. Eng. Asp.
Volume726
DOIs
StatePublished - 5 Dec 2025

    Research areas

  • Carrageenan, Chitosan, Colistin, Cyanocobalamin, Intestinal permeability, Polyelectrolyte complexes, Antibiotics, Binding energy, Cell culture, Controlled drug delivery, Hyaluronic acid, Monolayers, Multilayers, Targeted drug delivery, Toxicity, Bacterial infections, Carrageenans, Hydrodynamic diameter, Intestinal permeabilities, Multidrug resistants, Nephrotoxicity, Neurotoxicity, carrageenan, chitosan, colistin, cyanocobalamin, hyaluronic acid, nanocarrier, polyelectrolyte, polysaccharide, acute toxicity, animal experiment, animal tissue, antibacterial activity, antimicrobial activity, Article, association constant, binding affinity, Caco-2 cell line, chemical structure, controlled study, cytotoxicity, drug blood level, drug delivery system, Gram negative infection, HEK293 cell line, human, human cell, hydrodynamics, in vivo study, intestine mucosa permeability, male, minimum inhibitory concentration, multidrug resistant Gram negative bacterium, nephrotoxicity, neurotoxicity, nonhuman, particle size, Pseudomonas aeruginosa, rat, rodent model, structure analysis, sustained drug release, T98G cell line, zeta potential

ID: 143195033