{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:45:36Z","timestamp":1777502736365,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-73-20157-P"],"award-info":[{"award-number":["19-73-20157-P"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polymeric drug delivery systems enhance the biopharmaceutical properties of antibiotics by increasing their bioavailability, providing programmable and controlled-release properties, and reducing toxicity. In addition, drug delivery systems are a promising strategy to improve the intestinal permeability of various antimicrobial agents, including colistin (CT). This study describes the modification of conjugates based on CT and hyaluronic acid (HA) with cyanocobalamin (vitamin B12). Vitamin B12 was chosen as a targeting ligand because it has its own absorption pathway in the small intestine. The resulting polysaccharide conjugates contained 95 \u03bcg\/mg vitamin B12 and the CT content was 335 \u03bcg\/mg; they consisted of particles of two sizes, 98 and 702 nm, with a \u03b6-potential of approximately \u221225 mV. An in vitro release test at pH 7.4 and pH 5.2 showed an ultra-slow release of colistin of approximately 1% after 10 h. The modified B12 conjugates retained their antimicrobial activity at the level of pure CT (minimum inhibitory concentration was 2 \u03bcg\/mL). The resulting delivery systems also reduced the nephrotoxicity of CT by 30\u201340% (HEK 293 cell line). In addition, the modification of B12 improved the intestinal permeability of CT, and the apparent permeability coefficient of HA\u2013CT\u2013B12 conjugates was 3.5 \u00d7 10\u22126 cm\/s, corresponding to an in vivo intestinal absorption of 50\u2013100%. Thus, vitamin-B12-modified conjugates based on CT and HA may be promising oral delivery systems with improved biopharmaceutical properties.<\/jats:p>","DOI":"10.3390\/ijms241411550","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T01:31:32Z","timestamp":1689643892000},"page":"11550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cyanocobalamin-Modified Colistin\u2013Hyaluronan Conjugates: Synthesis and Bioactivity"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4399-9374","authenticated-orcid":false,"given":"Natallia V.","family":"Dubashynskaya","sequence":"first","affiliation":[{"name":"Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi VO 31, St. Petersburg 199004, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3355-2050","authenticated-orcid":false,"given":"Anton N.","family":"Bokatyi","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi VO 31, St. Petersburg 199004, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana S.","family":"Sall","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, Acad. Pavlov St. 12, St. Petersburg 197376, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana S.","family":"Egorova","sequence":"additional","affiliation":[{"name":"State Research Institute of Highly Pure Biopreparations, Pudozhsakya 7, St. Petersburg 197110, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuliya A.","family":"Nashchekina","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky 4, St. Petersburg 194064, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4510-5327","authenticated-orcid":false,"given":"Yaroslav A.","family":"Dubrovskii","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, Akkuratova 2, St. Petersburg 197341, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8723-8622","authenticated-orcid":false,"given":"Ekaterina A.","family":"Murashko","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, Akkuratova 2, St. Petersburg 197341, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena N.","family":"Vlasova","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi VO 31, St. Petersburg 199004, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena V.","family":"Demyanova","sequence":"additional","affiliation":[{"name":"State Research Institute of Highly Pure Biopreparations, Pudozhsakya 7, St. Petersburg 197110, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9731-6399","authenticated-orcid":false,"given":"Yury A.","family":"Skorik","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi VO 31, St. Petersburg 199004, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2174\/1570193X17999200529100808","article-title":"A comprehensive review on strategies for new drug discovery and enhanced productivity in research and development: Recent advancements and future prospectives","volume":"18","author":"Sharma","year":"2021","journal-title":"Mini Rev. 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