TY - JOUR

T1 - Hybrid Nanoparticles and Composite Hydrogel Systems for Delivery of Peptide Antibiotics

AU - Iudin, Dmitrii

AU - Vasilieva, Marina

AU - Knyazeva, Elena

AU - Korzhikov-Vlakh, Viktor

AU - Demyanova, Elena

AU - Lavrentieva, Antonina

AU - Skorik, Yury

AU - Korzhikova-Vlakh, Evgenia

N1 - Funding Information: This research was funded by the Russian Science Foundation (project no. 19-73-20157).

PY - 2022/3/2

Y1 - 2022/3/2

N2 - The growing number of drug-resistant pathogenic bacteria poses a global threat to human health. For this reason, the search for ways to enhance the antibacterial activity of existing antibiotics is now an urgent medical task. The aim of this study was to develop novel delivery systems for polymyxins to improve their antimicrobial properties against various infections. For this, hybrid core–shell nanoparticles, consisting of silver core and a poly(glutamic acid) shell capable of poly-myxin binding, were developed and carefully investigated. Characterization of the hybrid nanopar-ticles revealed a hydrodynamic diameter of approximately 100 nm and a negative electrokinetic potential. The nanoparticles demonstrated a lack of cytotoxicity, a low uptake by macrophages, and their own antimicrobial activity. Drug loading and loading efficacy were determined for both pol-ymyxin B and E, and the maximal loaded value with an appropriate size of the delivery systems was 450 µg/mg of nanoparticles. Composite materials based on agarose hydrogel were prepared, containing both the loaded hybrid systems and free antibiotics. The features of polymyxin release from the hybrid nanoparticles and the composite materials were studied, and the mechanisms of release were analyzed using different theoretical models. The antibacterial activity against Pseudo-monas aeruginosa was evaluated for both the polymyxin hybrid and the composite delivery systems. All tested samples inhibited bacterial growth. The minimal inhibitory concentrations of the poly-myxin B hybrid delivery system demonstrated a synergistic effect when compared with either the antibiotic or the silver nanoparticles alone.

AB - The growing number of drug-resistant pathogenic bacteria poses a global threat to human health. For this reason, the search for ways to enhance the antibacterial activity of existing antibiotics is now an urgent medical task. The aim of this study was to develop novel delivery systems for polymyxins to improve their antimicrobial properties against various infections. For this, hybrid core–shell nanoparticles, consisting of silver core and a poly(glutamic acid) shell capable of poly-myxin binding, were developed and carefully investigated. Characterization of the hybrid nanopar-ticles revealed a hydrodynamic diameter of approximately 100 nm and a negative electrokinetic potential. The nanoparticles demonstrated a lack of cytotoxicity, a low uptake by macrophages, and their own antimicrobial activity. Drug loading and loading efficacy were determined for both pol-ymyxin B and E, and the maximal loaded value with an appropriate size of the delivery systems was 450 µg/mg of nanoparticles. Composite materials based on agarose hydrogel were prepared, containing both the loaded hybrid systems and free antibiotics. The features of polymyxin release from the hybrid nanoparticles and the composite materials were studied, and the mechanisms of release were analyzed using different theoretical models. The antibacterial activity against Pseudo-monas aeruginosa was evaluated for both the polymyxin hybrid and the composite delivery systems. All tested samples inhibited bacterial growth. The minimal inhibitory concentrations of the poly-myxin B hybrid delivery system demonstrated a synergistic effect when compared with either the antibiotic or the silver nanoparticles alone.

KW - Antibiotics

KW - Antimicrobial properties

KW - Colistin

KW - Composite materials

KW - Core–shell structures

KW - Drug delivery systems

KW - Hybrid nanoparticles

KW - Peptides

KW - Polymyxin

UR - http://www.scopus.com/inward/record.url?scp=85125417388&partnerID=8YFLogxK

U2 - 10.3390/ijms23052771

DO - 10.3390/ijms23052771

M3 - Article

C2 - 35269910

AN - SCOPUS:85125417388

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 5

M1 - 2771

ER -