| Autor: |
Stepanova M; Institute of Macromolecular Compounds of Russian Academy of Sciences, 199004 St. Petersburg, Russia., Levit M; Institute of Macromolecular Compounds of Russian Academy of Sciences, 199004 St. Petersburg, Russia., Egorova T; Institute of Highly Pure Biopreparations, 197110 St. Petersburg, Russia., Nashchekina Y; Institute of Cytology of Russian Academy of Sciences, 194064 St. Petersburg, Russia., Sall T; Institute of Experimental Medicine, 197022 St. Petersburg, Russia., Demyanova E; Institute of Highly Pure Biopreparations, 197110 St. Petersburg, Russia., Guryanov I; Institute of Chemistry, St. Petersburg State University, 198504 St. Petersburg, Russia., Korzhikova-Vlakh E; Institute of Macromolecular Compounds of Russian Academy of Sciences, 199004 St. Petersburg, Russia. |
| Jazyk: |
angličtina |
| Zdroj: |
Pharmaceutics [Pharmaceutics] 2024 Aug 17; Vol. 16 (8). Date of Electronic Publication: 2024 Aug 17. |
| DOI: |
10.3390/pharmaceutics16081080 |
| Abstrakt: |
Growing resistance to traditional antibiotics poses a global threat to public health. In this regard, modification of known antibiotics, but with limited applications due to side effects, is one of the extremely promising approaches at present. In this study, we proposed the synthesis of novel complex polymeric conjugates of the peptide antibiotic colistin (CT). A biocompatible and water-soluble synthetic glycopolymer, namely, poly(2-deoxy-2-methacrylamido- D -glucose) (PMAG), was used as a polymer carrier. In addition to monoconjugates containing CT linked to PMAG by hydrolyzable and stable bonds, a set of complex conjugates also containing the siderophore deferoxamine (DFOA) and vitamin B12 was developed. The structures of the conjugates were confirmed by 1 H NMR and FTIR-spectroscopy, while the compositions of conjugates were determined by UV-Vis spectrophotometry and HPLC analysis. The buffer media with pH 7.4, corresponding to blood or ileum pH, and 5.2, corresponding to the intestinal pH after ingestion or pH in the focus of inflammation, were used to study the release of CT. The resulting conjugates were examined for cytotoxicity and antimicrobial activity. All conjugates showed less cytotoxicity than free colistin. A Caco-2 cell permeability assay was carried out for complex conjugates to simulate the drug absorption in the intestine. In contrast to free CT, which showed very low permeability through the Caco-2 monolayer, the complex polymeric conjugates of vitamin B12 and CT provided significant transport. The antimicrobial activity of the conjugates depended on the conjugate composition. It was found that conjugates containing CT linked to the polymer by a hydrolyzable bond were found to be more active than conjugates with a non-hydrolyzable bond between CT and PMAG. Conjugates containing DFOA complexed with Fe 3+ were characterized by enhanced antimicrobial activity against Pseudomonas aeruginosa compared to other conjugates. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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