TY - JOUR

T1 - Carrageenan and cyanocobalamin-chitosan based nanoantibiotics: An effective strategy for colistin delivery

AU - Dubashynskaya, N.V.

AU - Zhuravskii, S.G.

AU - Borovskoy, A.Y.

AU - Bokatyi, A.N.

AU - Sall, T.S.

AU - Egorova, T.S.

AU - Demyanova, E.V.

AU - Murashko, E.A.

AU - Mukhametdinova, D.V.

AU - Shasherina, A.Y.

AU - Anufrikov, Y.A.

AU - Skorik, Y.A.

N1 - Export Date: 01 November 2025; Cited By: 0; Correspondence Address: Y.A. Skorik; Branch of Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute» – Institute of Macromolecular Compounds, St. Petersburg, Bolshoi VO 31, 199004, Russian Federation; email: yury_skorik@mail.ru; CODEN: CPEAE

PY - 2025/12/5

Y1 - 2025/12/5

N2 - 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.

AB - 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.

KW - Carrageenan

KW - Chitosan

KW - Colistin

KW - Cyanocobalamin

KW - Intestinal permeability

KW - Polyelectrolyte complexes

KW - Antibiotics

KW - Binding energy

KW - Cell culture

KW - Controlled drug delivery

KW - Hyaluronic acid

KW - Monolayers

KW - Multilayers

KW - Targeted drug delivery

KW - Toxicity

KW - Bacterial infections

KW - Carrageenans

KW - Hydrodynamic diameter

KW - Intestinal permeabilities

KW - Multidrug resistants

KW - Nephrotoxicity

KW - Neurotoxicity

KW - carrageenan

KW - chitosan

KW - colistin

KW - cyanocobalamin

KW - hyaluronic acid

KW - nanocarrier

KW - polyelectrolyte

KW - polysaccharide

KW - acute toxicity

KW - animal experiment

KW - animal tissue

KW - antibacterial activity

KW - antimicrobial activity

KW - Article

KW - association constant

KW - binding affinity

KW - Caco-2 cell line

KW - chemical structure

KW - controlled study

KW - cytotoxicity

KW - drug blood level

KW - drug delivery system

KW - Gram negative infection

KW - HEK293 cell line

KW - human

KW - human cell

KW - hydrodynamics

KW - in vivo study

KW - intestine mucosa permeability

KW - male

KW - minimum inhibitory concentration

KW - multidrug resistant Gram negative bacterium

KW - nephrotoxicity

KW - neurotoxicity

KW - nonhuman

KW - particle size

KW - Pseudomonas aeruginosa

KW - rat

KW - rodent model

KW - structure analysis

KW - sustained drug release

KW - T98G cell line

KW - zeta potential

UR - https://www.mendeley.com/catalogue/4656747b-3397-3d49-b006-92f781a00025/

U2 - 10.1016/j.colsurfa.2025.137788

DO - 10.1016/j.colsurfa.2025.137788

M3 - статья

VL - 726

JO - Colloids and Surfaces A: Physicochemical and Engineering Aspects

JF - Colloids and Surfaces A: Physicochemical and Engineering Aspects

SN - 0927-7757

M1 - 137788

ER -