{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T10:45:41Z","timestamp":1782297941114,"version":"3.54.5"},"reference-count":81,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"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"],"award-info":[{"award-number":["19-73-20157"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 1H NMR and FTIR-spectroscopy, while the compositions of conjugates were determined by UV\u2013Vis 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 Fe3+ were characterized by enhanced antimicrobial activity against Pseudomonas aeruginosa compared to other conjugates.<\/jats:p>","DOI":"10.3390\/pharmaceutics16081080","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T03:43:28Z","timestamp":1724039008000},"page":"1080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Poly(2-Deoxy-2-Methacrylamido-D-Glucose)-Based Complex Conjugates of Colistin, Deferoxamine and Vitamin B12: Synthesis and Biological Evaluation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-4321","authenticated-orcid":false,"given":"Mariia","family":"Stepanova","sequence":"first","affiliation":[{"name":"Institute of Macromolecular Compounds of Russian Academy of Sciences, 199004 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2136-1329","authenticated-orcid":false,"given":"Mariia","family":"Levit","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Compounds of Russian Academy of Sciences, 199004 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Egorova","sequence":"additional","affiliation":[{"name":"Institute of Highly Pure Biopreparations, 197110 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Nashchekina","sequence":"additional","affiliation":[{"name":"Institute of Cytology of Russian Academy of Sciences, 194064 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5890-5641","authenticated-orcid":false,"given":"Tatiana","family":"Sall","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, 197022 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Demyanova","sequence":"additional","affiliation":[{"name":"Institute of Highly Pure Biopreparations, 197110 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6897-3528","authenticated-orcid":false,"given":"Ivan","family":"Guryanov","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, St. Petersburg State University, 198504 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2530-7709","authenticated-orcid":false,"given":"Evgenia","family":"Korzhikova-Vlakh","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Compounds of Russian Academy of Sciences, 199004 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"ref_1","unstructured":"(2024, August 16). Critically Important Antimicrobials for Human Medicine. Available online: http:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/77376\/9789241504485_eng.pdf?sequence=1."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.bioorg.2017.11.007","article-title":"Amino acids\/peptides conjugated heterocycles: A tool for the recent development of novel therapeutic agents","volume":"76","author":"Wang","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113818","DOI":"10.1016\/j.addr.2021.05.028","article-title":"Antimicrobial peptides towards clinical application: Delivery and formulation","volume":"175","author":"Wang","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mohapatra, S.S., Dwibedy, S.K., and Padhy, I. (2021). Polymyxins, the last-resort antibiotics: Mode of action, resistance emergence, and potential solutions. J. Biosci., 46.","DOI":"10.1007\/s12038-021-00209-8"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"711","DOI":"10.2217\/fmb.13.39","article-title":"Pharmacology of polymyxins: New insights into an \u2019old class of antibiotics","volume":"8","author":"Velkov","year":"2013","journal-title":"Future Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a025288","DOI":"10.1101\/cshperspect.a025288","article-title":"Polymyxin: Alternative Mechanisms of Action and Resistance","volume":"6","author":"Trimble","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1586\/14787210.2015.1093933","article-title":"Polymyxin B versus colistin: An update","volume":"13","author":"Cai","year":"2015","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.pharmthera.2017.07.012","article-title":"Polymyxins for CNS infections: Pharmacology and neurotoxicity","volume":"181","author":"Velkov","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1086\/429323","article-title":"Colistin: The Revival of Polymyxins for the Management of Multidrug-Resistant Gram-Negative Bacterial Infections","volume":"40","author":"Falagas","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dubashynskaya, N.V., and Skorik, Y.A. (2020). Polymyxin Delivery Systems: Recent Advances and Challenges. Pharmaceuticals, 13.","DOI":"10.3390\/ph13050083"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Iudin, D., Zashikhina, N., Demyanova, E., Korzhikov-Vlakh, V., Shcherbakova, E., Boroznjak, R., Tarasenko, I., Zakharova, N., Lavrentieva, A., and Skorik, Y. (2020). Polypeptide self-assembled nanoparticles as delivery systems for polymyxins B and E. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090868"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"122739","DOI":"10.1016\/j.ijpharm.2023.122739","article-title":"Colistin- and amikacin-loaded lipid-based drug delivery systems for resistant gram-negative lung and wound bacterial infections","volume":"635","author":"Vairo","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1900564","DOI":"10.1002\/adhm.201900564","article-title":"Bioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by Salmonella enterica","volume":"8","author":"Menina","year":"2019","journal-title":"Adv. Healthc. Mater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.xphs.2018.11.032","article-title":"Bioavailability Enhancement of Polymyxin B With Novel Drug Delivery: Development and Optimization Using Quality-by-Design Approach","volume":"108","author":"Chauhan","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ijbiomac.2021.07.114","article-title":"Hyaluronan\/colistin polyelectrolyte complexes: Promising antiinfective drug delivery systems","volume":"187","author":"Dubashynskaya","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dubashynskaya, N.V., Raik, S.V., Dubrovskii, Y.A., Demyanova, E.V., Shcherbakova, E.S., Poshina, D.N., Shasherina, A.Y., Anufrikov, Y.A., and Skorik, Y.A. (2021). Hyaluronan\/Diethylaminoethyl Chitosan Polyelectrolyte Complexes as Carriers for Improved Colistin Delivery. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168381"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1134\/S0965545X20010125","article-title":"Multilayered Particles Based on Biopolyelectrolytes as Potential Peptide Delivery Systems","volume":"62","author":"Zashikhina","year":"2020","journal-title":"Polym. Sci. Ser. A"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Stepanova, M., Nikiforov, A., Tennikova, T., and Korzhikova-Vlakh, E. (2023). Polypeptide-Based Systems: From Synthesis to Application in Drug Delivery. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112641"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.actbio.2018.10.013","article-title":"Colistin nanoparticle assembly by coacervate complexation with polyanionic peptides for treating drug-resistant gram-negative bacteria","volume":"82","author":"Liu","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yasar, H., Ho, D.-K., De Rossi, C., Herrmann, J., Gordon, S., Loretz, B., and Lehr, C.-M. (2018). Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery. Polymers, 10.","DOI":"10.3390\/polym10030252"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ijpharm.2009.10.026","article-title":"Cellular uptake and toxicity of microparticles in a perspective of polymyxin B oral administration","volume":"385","author":"Coppi","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1080\/02652040400015437","article-title":"Alginate microparticles for Polymyxin B Peyer\u2019s patches uptake: Microparticles for antibiotic oral administration","volume":"21","author":"Coppi","year":"2004","journal-title":"J. Microencapsul."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Iudin, D., Vasilieva, M., Knyazeva, E., Korzhikov-Vlakh, V., Demyanova, E., Lavrentieva, A., Skorik, Y., and Korzhikova-Vlakh, E. (2022). Hybrid Nanoparticles and Composite Hydrogel Systems for Delivery of Peptide Antibiotics. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052771"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1080\/02652048.2016.1242665","article-title":"Stability study of sodium colistimethate-loaded lipid nanoparticles","volume":"33","author":"Pastor","year":"2016","journal-title":"J. Microencapsul."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ejps.2017.05.063","article-title":"Antimicrobial activity of polymyxin-loaded solid lipid nanoparticles (PLX-SLN): Characterization of physicochemical properties and in vitro efficacy","volume":"106","author":"Severino","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Costa, J.S.R., Medeiros, M., Yamashiro-Kanashiro, E.H., Rocha, M.C., Cotrim, P.C., Stephano, M.A., Lancellotti, M., Tavares, G.D., and Oliveira-Nascimento, L. (2019). Biodegradable nanocarriers coated with polymyxin b: Evaluation of leishmanicidal and antibacterial potential. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007388"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1177\/0885328215593837","article-title":"Poly(l-lactide)\/halloysite nanotube electrospun mats as dual-drug delivery systems and their therapeutic efficacy in infected full-thickness burns","volume":"30","author":"Zhang","year":"2015","journal-title":"J. Biomater. Appl."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chiron, E., Varache, M., Stokniene, J., Thomas, D.W., and Ferguson, E.L. (2021). A physicochemical assessment of the thermal stability of dextrin\u2013colistin conjugates. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-89946-2"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1021\/mp500584u","article-title":"Dextrin\u2013Colistin Conjugates as a Model Bioresponsive Treatment for Multidrug Resistant Bacterial Infections","volume":"11","author":"Ferguson","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Stokniene, J., Powell, L.C., Aarstad, O.A., Aachmann, F.L., Rye, P.D., Hill, K.E., Thomas, D.W., and Ferguson, E.L. (2020). Bi-Functional Alginate Oligosaccharide\u2013Polymyxin Conjugates for Improved Treatment of Multidrug-Resistant Gram-Negative Bacterial Infections. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111080"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jconrel.2017.02.005","article-title":"A traceless reversible polymeric colistin prodrug to combat multidrug-resistant (MDR) gram-negative bacteria","volume":"259","author":"Zhu","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1021\/acs.bioconjchem.7b00242","article-title":"Hydrolyzable Poly[Poly(Ethylene Glycol) Methyl Ether Acrylate]\u2013Colistin Prodrugs through Copper-Mediated Photoinduced Living Radical Polymerization","volume":"28","author":"Zhu","year":"2017","journal-title":"Bioconjug. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ijbiomac.2022.06.080","article-title":"Hyaluronan-colistin conjugates: Synthesis, characterization, and prospects for medical applications","volume":"215","author":"Dubashynskaya","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1128\/AAC.42.3.583","article-title":"Covalent Polymyxin B Conjugate with Human Immunoglobulin G as an Antiendotoxin Reagent","volume":"42","author":"Drabick","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1021\/acsinfecdis.1c00318","article-title":"Vancomyxins: Vancomycin-Polymyxin Nonapeptide Conjugates That Retain Anti-Gram-Positive Activity with Enhanced Potency against Gram-Negative Strains","volume":"7","author":"Slingerland","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dubashynskaya, N.V., Bokatyi, A.N., Dobrodumov, A.V., Kudryavtsev, I.V., Trulioff, A.S., Rubinstein, A.A., Aquino, A.D., Dubrovskii, Y.A., Knyazeva, E.S., and Demyanova, E.V. (2022). Succinyl Chitosan-Colistin Conjugates as Promising Drug Delivery Systems. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010166"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Dvoretckaia, A., Egorova, T., Dzhuzha, A., Levit, M., Sivtsov, E., Demyanova, E., and Korzhikova-Vlakh, E. (2023). Polymyxin B Conjugates with Bio-Inspired Synthetic Polymers of Different Nature. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031832"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1021\/acs.jmedchem.5b01521","article-title":"In Vitro Evaluation of the Interaction of Dextrin\u2013Colistin Conjugates with Bacterial Lipopolysaccharide","volume":"59","author":"Roberts","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1007\/s10311-019-00887-9","article-title":"Advances in the antimicrobial and therapeutic potential of siderophores","volume":"17","author":"Ribeiro","year":"2019","journal-title":"Environ. Chem. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.molmed.2016.10.005","article-title":"Siderophores in Iron Metabolism: From Mechanism to Therapy Potential","volume":"22","author":"Wilson","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Negash, K.H., Norris, J.K., and Hodgkinson, J.T. (2019). Siderophore\u2013Antibiotic Conjugate Design: New Drugs for Bad Bugs?. Molecules, 24.","DOI":"10.3390\/molecules24183314"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.bmc.2012.10.028","article-title":"Synthesis and antibacterial activity of conjugates between norfloxacin and analogues of the siderophore vanchrobactin","volume":"21","author":"Souto","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21310","DOI":"10.1021\/jacs.0c06987","article-title":"Platform to Discover Protease-Activated Antibiotics and Application to Siderophore\u2013Antibiotic Conjugates","volume":"142","author":"Boyce","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1021\/bc300610f","article-title":"Trihydroxamate Siderophore\u2013Fluoroquinolone Conjugates Are Selective Sideromycin Antibiotics that Target Staphylococcus aureus","volume":"24","author":"Wencewicz","year":"2013","journal-title":"Bioconjug. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1002\/anie.200800865","article-title":"Traveling the Vitamin B 12 Pathway: Oral Delivery of Protein and Peptide Drugs","volume":"48","author":"Petrus","year":"2009","journal-title":"Angew. Chemie Int. Ed."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Fedosov, S.N. (2012). Physiological and Molecular Aspects of Cobalamin Transport. Water Soluble Vitamins, Springer.","DOI":"10.1007\/978-94-007-2199-9_18"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ejpb.2012.11.024","article-title":"Development and in vivo evaluation of an oral vitamin B12 delivery system","volume":"84","author":"Sarti","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.ijbiomac.2021.02.093","article-title":"Low molecular weight chitosan-cyanocobalamin nanoparticles for controlled delivery of ciprofloxacin: Preparation and evaluation","volume":"176","author":"Tadjarodi","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.jconrel.2006.12.003","article-title":"A novel vitamin B12-nanosphere conjugate carrier system for peroral delivery of insulin","volume":"117","author":"Chalasani","year":"2007","journal-title":"J. Control. Release"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.actbio.2015.12.017","article-title":"Vitamin B12 functionalized layer by layer calcium phosphate nanoparticles: A mucoadhesive and pH responsive carrier for improved oral delivery of insulin","volume":"31","author":"Verma","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dubashynskaya, N.V., Bokatyi, A.N., Sall, T.S., Egorova, T.S., Nashchekina, Y.A., Dubrovskii, Y.A., Murashko, E.A., Vlasova, E.N., Demyanova, E.V., and Skorik, Y.A. (2023). Cyanocobalamin-Modified Colistin\u2013Hyaluronan Conjugates: Synthesis and Bioactivity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411550"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1002\/app.27292","article-title":"Water-soluble aldehyde-bearing polymers of 2-deoxy-2-methacrylamido-D- glucose for bone tissue engineering","volume":"108","author":"Korzhikov","year":"2008","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1021\/bc700383w","article-title":"Synthesis of Multifunctional Polyvinylsaccharide Containing Controllable Amounts of Biospecific Ligands","volume":"19","author":"Korzhikov","year":"2008","journal-title":"Bioconjug. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Miller, S.J., and Morgan, B.W. (2014). Deferoxamine. Encyclopedia of Toxicology, Elsevier.","DOI":"10.1016\/B978-0-12-386454-3.00721-1"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.eurpolymj.2018.05.018","article-title":"Synthesis and characterization of well-defined poly(2-deoxy-2-methacrylamido-d-glucose) and its biopotential block copolymers via RAFT and ROP polymerization","volume":"105","author":"Levit","year":"2018","journal-title":"Eur. Polym. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.carbpol.2018.03.080","article-title":"Mutlifunctional nanoparticles prepared from arginine-modified chitosan and thiolated fucoidan for oral delivery of hydrophobic and hydrophilic drugs","volume":"193","author":"Chen","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1039\/C5OB00780A","article-title":"Studies on tridecaptin B 1, a lipopeptide with activity against multidrug resistant Gram-negative bacteria","volume":"13","author":"Cochrane","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/(SICI)1097-0282(199703)41:3<251::AID-BIP2>3.0.CO;2-R","article-title":"Polymyxin B nonapeptide: Conformations in water and in the lipopolysaccharide-bound state determined by two-dimensional NMR and molecular dynamics","volume":"41","author":"Bhattacharjya","year":"1997","journal-title":"Biopolymers"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11010","DOI":"10.1074\/jbc.275.15.11010","article-title":"Purification and Structural Determination of SCB1, a \u03b3-Butyrolactone That Elicits Antibiotic Production inStreptomyces coelicolor A3(2)","volume":"275","author":"Takano","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Yu, B., Yang, Y., Liu, Q., Zhan, A., Yang, Y., and Liu, H. (2020). A Novel Star Like Eight-Arm Polyethylene Glycol-Deferoxamine Conjugate for Iron Overload Therapy. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12040329"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Muenraya, P., Sawatdee, S., Srichana, T., and Atipairin, A. (2022). Silver Nanoparticles Conjugated with Colistin Enhanced the Antimicrobial Activity against Gram-Negative Bacteria. Molecules, 27.","DOI":"10.3390\/molecules27185780"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Solomakha, O., Stepanova, M., Dobrodumov, A., Gofman, I., Nashchekina, Y., Nashchekin, A., and Korzhikova-Vlakh, E. (2024). Chemical Modification of Nanocrystalline Cellulose for Manufacturing of Osteoconductive Composite Materials. Polymers, 16.","DOI":"10.3390\/polym16131936"},{"key":"ref_63","unstructured":"Socrates, G. (2004). Infrared and Raman Characteristic Group Frequencies: Tables and Charts, Wiley. [3rd ed.]."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jgar.2018.01.005","article-title":"Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains","volume":"13","author":"Shahzad","year":"2018","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/phar.1493","article-title":"Adverse reactions associated with systemic polymyxin therapy","volume":"35","author":"Juston","year":"2015","journal-title":"Pharmacotherapy"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/S0026-0495(96)90171-7","article-title":"Effects of vitamin B12 on cell proliferation and cellular alkaline phosphatase activity in human bone marrow stromal osteoprogenitor cells and UMR106 osteoblastic cells","volume":"45","author":"Kim","year":"1996","journal-title":"Metabolism"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1155\/2006\/901873","article-title":"Colistin: The phoenix Arises","volume":"17","author":"Conly","year":"2006","journal-title":"Can. J. Infect. Dis. Med. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/bs.vh.2022.01.016","article-title":"Vitamin B12 absorption and malabsorption","volume":"119","author":"Alpers","year":"2022","journal-title":"Vitam. Horm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/nprot.2007.303","article-title":"Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers","volume":"2","author":"Hubatsch","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lea, T. (2015). Caco-2 Cell Line. The Impact of Food Bioactives on Health, Springer International Publishing.","DOI":"10.1007\/978-3-319-16104-4_10"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/BF00756522","article-title":"The human intestinal epithelial cell line Caco-2; pharmacological and pharmacokinetic applications","volume":"11","author":"Meunier","year":"1995","journal-title":"Cell Biol. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0144-8617(01)00263-6","article-title":"The use of polysaccharides to target drugs to the colon","volume":"48","author":"Vandamme","year":"2002","journal-title":"Carbohydr. Polym."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1021\/mp100149j","article-title":"Physiological Parameters for Oral Delivery and in Vitro Testing","volume":"7","author":"Mudie","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0731-7085(02)00016-X","article-title":"Study of the stability of polymyxins B1, E1 and E2 in aqueous solution using liquid chromatography and mass spectrometry","volume":"29","author":"Orwa","year":"2002","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.biochi.2012.11.004","article-title":"Vitamin B12 absorption: Mammalian physiology and acquired and inherited disorders","volume":"95","author":"Kozyraki","year":"2013","journal-title":"Biochimie"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"13410","DOI":"10.1074\/jbc.M112.426254","article-title":"Extracellular Acidosis Is a Novel Danger Signal Alerting Innate Immunity via the NLRP3 Inflammasome","volume":"288","author":"Nurmi","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1021\/jo01360a019","article-title":"Reduction of Schiff Bases with Sodium Borohydride","volume":"22","author":"Billman","year":"1957","journal-title":"J. Org. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1021\/jo00442a034","article-title":"Reduction of sterigmatocystin and versicolorin A hemiacetals with sodium borohydride","volume":"42","author":"Chen","year":"1977","journal-title":"J. Org. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1039\/p19860000055","article-title":"Reduction of hemiacetal ring-opened forms of Asclepiadaceae cardenolide glycosides","volume":"1","author":"Cheung","year":"1986","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1021\/jo00924a006","article-title":"Hemiacetal mediated reactions. Directed synthesis of diols and acetals","volume":"39","author":"Overman","year":"1974","journal-title":"J. Org. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"114162","DOI":"10.1016\/j.poly.2019.114162","article-title":"Use of 13C and 1H NMR to determine in detail the structures of the base-off vitamin B12 complexes dicyanocobinamide and dicyanocobalamin","volume":"174","author":"Chemaly","year":"2019","journal-title":"Polyhedron"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/8\/1080\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:38:11Z","timestamp":1760110691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/8\/1080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,17]]},"references-count":81,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["pharmaceutics16081080"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16081080","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,17]]}}}