{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:07:03Z","timestamp":1790737623062,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"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":["22-24-00604"],"award-info":[{"award-number":["22-24-00604"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Bacterial infections are usually found in the stomach and the first part of the small intestine in association with various pathologies, including ulcers, inflammatory diseases, and sometimes cancer. Treatment options may include combinations of antibiotics with proton pump inhibitors and anti-inflammatory drugs. However, all of them have high systemic exposure and, hence, unfavorable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is limited. Chitosan and nanogels based on chitosan presumably are not absorbed from the gastrointestinal tract and are known to adhere to the mucus. Therefore, they can serve as a basis for the local delivery of antibacterial drugs, increasing their exposure at the predominant location of therapeutic targets, thus improving the risk\/benefit ratio. We have used E. coli ATCC 25922 (as a screening model of pathogenic bacteria) and Lactobacilli (as a model of a normal microbiome) to study the antibacterial activity of antibacterial drugs entrapped in a chitosan nanogel. Classical antibiotics were studied in a monotherapeutic regimen as well as in combination with individual terpenoids and flavonoids as adjuvants. It has been shown that levofloxacin (LF) in combination with zephirol demonstrate synergistic effects against E. coli (cell viability decreased by about 50%) and, surprisingly, a much weaker effect against Lactobacilli. A number of other combinations of antibiotic + adjuvant were also shown to be effective. Using FTIR and UV spectroscopy, it has been confirmed that chitosan nanogels with the drug are well adsorbed on the mucosal model, providing prolonged release at the target location. Using an ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which are potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. In vivo experiments (on sturgeon fish) showed the effective action of antibacterial formulations developed based on LF in chitosan nanogels for up to 11 days. Thus, chitosan nanogels loaded with a combination of drugs and adjuvants can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract.<\/jats:p>","DOI":"10.3390\/pharmaceutics15092353","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T21:47:03Z","timestamp":1695246423000},"page":"2353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mucosal Adhesive Chitosan Nanogel Formulations of Antibiotics and Adjuvants (Terpenoids, Flavonoids, etc.) and Their Potential for the Treatment of Infectious Diseases of the Gastrointestinal Tract"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-0859","authenticated-orcid":false,"given":"Igor D.","family":"Zlotnikov","sequence":"first","affiliation":[{"name":"Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1\/3, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya G.","family":"Belogurova","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1\/3, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina V.","family":"Poddubnaya","sequence":"additional","affiliation":[{"name":"Research Laboratory of Aquatic Environment Protection and Ichthyopathology, Saratov State University of Genetics, Biotechnology and Engineering Named after N.I. Vavilov, 410005 Saratov, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9761-7757","authenticated-orcid":false,"given":"Elena V.","family":"Kudryashova","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1\/3, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s43188-019-00024-2","article-title":"Phylogenetic evidence revealed Cantharocybe virosa (Agaricales, Hygrophoraceae) as a new clinical record for gastrointestinal mushroom poisoning in Thailand","volume":"36","author":"Parnmen","year":"2020","journal-title":"Toxicol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1080\/15563650.2021.1961144","article-title":"Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose","volume":"59","author":"Hoegberg","year":"2021","journal-title":"Clin. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1053\/j.gastro.2018.01.045","article-title":"Best Practice Update: Incorporating Psychogastroenterology Into Management of Digestive Disorders","volume":"154","author":"Keefer","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_4","first-page":"659","article-title":"Cambios, dolencias funcionales y enfermedades en el sistema gastrointestinal en personas mayores","volume":"26","author":"Grassi","year":"2011","journal-title":"Nutr. Hosp."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41578-021-00362-4","article-title":"Biomaterial-based antimicrobial therapies for the treatment of bacterial infections","volume":"7","author":"Kalelkar","year":"2022","journal-title":"Nat. Rev. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1038\/s41598-021-82044-3","article-title":"Oral absorption and drug interaction kinetics of moxifloxacin in an animal model of weightlessness","volume":"11","author":"Liang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1128\/jcm.33.5.1203-1205.1995","article-title":"Cytotoxin production by Helicobacter pylori from patients with upper gastrointestinal tract diseases","volume":"33","author":"Tee","year":"1995","journal-title":"J. Clin. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/apt.12666","article-title":"Review article: Bacteria and pathogenesis of disease in the upper gastrointestinal tract\u2014Beyond the era of Helicobacter pylori","volume":"39","author":"Walker","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"176","DOI":"10.21518\/2079-701X-2021-15-176-183","article-title":"Dietary therapeutic and preventive food products in complex therapy of gastroinal tract diseases associated with Helicobacter pylori","volume":"2021","author":"Pilat","year":"2021","journal-title":"Meditsinskiy Sov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1007\/s13346-021-00913-w","article-title":"An overview of chitosan and its application in infectious diseases","volume":"11","author":"Meng","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.lwt.2012.11.011","article-title":"Characterization of beta-cyclodextrin inclusion complexes containing essential oils (trans-cinnamaldehyde, eugenol, cinnamon bark, and clove bud extracts) for antimicrobial delivery applications","volume":"51","author":"Hill","year":"2013","journal-title":"LWT-Food Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5647182","DOI":"10.1155\/2016\/5647182","article-title":"Synergism Effect of the Essential Oil from Ocimum basilicum var. Maria Bonita and Its Major Components with Fluconazole and Its Influence on Ergosterol Biosynthesis","volume":"2016","author":"Cardoso","year":"2016","journal-title":"Evidence-Based Complement. Altern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1271\/bbb.70264","article-title":"Dillapiol and apiol as specific inhibitors of the biosynthesis of aflatoxin G1 in Aspergillus parasiticus","volume":"71","author":"Yoshinari","year":"2007","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1007\/s11172-007-0389-1","article-title":"Polyalkoxybenzenes from plant raw materials 1. Isolation of polyalkoxybenzenes from CO2 extracts of Umbelliferae plant seeds","volume":"56","author":"Semenov","year":"2007","journal-title":"Russ. Chem. Bull."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., and Kudryashova, E.V. (2022). Spectroscopy Approach for Highly\u2014Efficient Screening of Lectin\u2014Ligand Interactions in Application for Mannose Receptor and Molecular Containers for Antibacterial Drugs. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050625"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1590\/S1516-93322007000100015","article-title":"Inhibitory effect of \u03b2-pinene, \u03b1-pinene and eugenol on the growth of potential infectious endocarditis causing Gram-positive bacteria","volume":"43","author":"Leite","year":"2007","journal-title":"Rev. Bras. Ciencias Farm. J. Pharm. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., Ezhov, A.A., Petrov, R.A., Vigovskiy, M.A., Grigorieva, O.A., Belogurova, N.G., and Kudryashova, E.V. (2022). Mannosylated Polymeric Ligands for Targeted Delivery of Antibacterials and Their Adjuvants to Macrophages for the Enhancement of the Drug Efficiency. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101172"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., Belogurova, N.G., Krylov, S.S., Semenova, M.N., Semenov, V.V., and Kudryashova, E.V. (2022). Plant Alkylbenzenes and Terpenoids in the Form of Cyclodextrin Inclusion Complexes as Antibacterial Agents and Levofloxacin Synergists. Pharmaceuticals, 15.","DOI":"10.3390\/ph15070861"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Valdivieso-Ugarte, M., Gomez-Llorente, C., Plaza-D\u00edaz, J., and Gil, \u00c1. (2019). Antimicrobial, antioxidant, and immunomodulatory properties of essential oils: A systematic review. Nutrients, 11.","DOI":"10.3390\/nu11112786"},{"key":"ref_20","first-page":"1","article-title":"Essential Oils and Future Antibiotics: New Weapons against Emerging\u2019Superbugs\u2019?","volume":"1","author":"Boire","year":"2013","journal-title":"J. Anc. Dis. Prev. Remedies"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1021\/acs.jnatprod.8b00878","article-title":"Antioxidant Activity of Natural Allylpolyalkoxybenzene Plant Essential Oil Constituents","volume":"82","author":"Samet","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.canlet.2004.11.018","article-title":"Eugenol isolated from the essential oil of Eugenia caryophyllata induces a reactive oxygen species-mediated apoptosis in HL-60 human promyelocytic leukemia cells","volume":"225","author":"Yoo","year":"2005","journal-title":"Cancer Lett."},{"key":"ref_23","first-page":"277","article-title":"Antimicrobial constituents and synergism effect of the essential oils from Cymbopogon citratus and Alpinia galanga","volume":"9","author":"Tadtong","year":"2014","journal-title":"Nat. Prod. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6663255","DOI":"10.1155\/2021\/6663255","article-title":"GC-MS Characterization of Antibacterial, Antioxidant, and Antitrypanosomal Activity of Syzygium aromaticum Essential Oil and Eugenol","volume":"2021","author":"Teles","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1472-765X.2010.02837.x","article-title":"Antimicrobial and antioxidant activities of Mexican oregano essential oils (Lippia graveolens H. B. K.) with different composition when microencapsulated in\u03b2-cyclodextrin","volume":"50","year":"2010","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00284-015-0933-4","article-title":"Linalool Affects the Antimicrobial Efficacy of Essential Oils","volume":"72","author":"Herman","year":"2016","journal-title":"Curr. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., Vigovskiy, M.A., Davydova, M.P., Danilov, M.R., Dyachkova, U.D., Grigorieva, O.A., and Kudryashova, E. (2022). V Mannosylated Systems for Targeted Delivery of Antibacterial Drugs to Activated Macrophages. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232416144"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: An overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ilyasov, I.R., Beloborodov, V.L., Selivanova, I.A., and Terekhov, R.P. (2020). ABTS\/PP decolorization assay of antioxidant capacity reaction pathways. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031131"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1002\/nano.202200049","article-title":"Bacteria (E. coli) take up ultrasmall gold nanoparticles (2 nm) as shown by different optical microscopic techniques (CLSM, SIM, STORM)","volume":"3","author":"Sokolova","year":"2022","journal-title":"Nano Sel."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1080\/10717544.2022.2058646","article-title":"Application of chitosan\/alginate nanoparticle in oral drug delivery systems: Prospects and challenges","volume":"29","author":"Li","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kumari, R., Gupta, S., Singh, A.R., Ferosekhan, S., Kothari, D.C., Pal, A.K., and Jadhao, S.B. (2013). Chitosan Nanoencapsulated Exogenous Trypsin Biomimics Zymogen-Like Enzyme in Fish Gastrointestinal Tract. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074743"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105466","DOI":"10.1016\/j.ejps.2020.105466","article-title":"Polymeric micelles based on amphiphilic oleic acid modified carboxymethyl chitosan for oral drug delivery of bcs class iv compound: Intestinal permeability and pharmacokinetic evaluation","volume":"153","author":"Kumar","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"110920","DOI":"10.1016\/j.msec.2020.110920","article-title":"Novel amphiphilic chitosan micelles as carriers for hydrophobic anticancer drugs","volume":"112","author":"Almeida","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1208\/s12249-010-9483-z","article-title":"Chitosan\/polyethylene glycol beads crosslinked with tripolyphosphate and glutaraldehyde for gastrointestinal drug delivery","volume":"11","author":"Buranachai","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.drudis.2015.03.002","article-title":"The design of pH-sensitive chitosan-based formulations for gastrointestinal delivery","volume":"20","author":"Du","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., Streltsov, D.A., Belogurova, N.G., and Kudryashova, E.V. (2023). Chitosan or Cyclodextrin Grafted with Oleic Acid Self-Assemble into Stabilized Polymeric Micelles with Potential of Drug Carriers. Life, 13.","DOI":"10.3390\/life13020446"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1042\/BJ20040402","article-title":"Effects of pH on Helicobacter pylori binding to human gastric mucins: Identification of binding to non-MUC5AC mucins","volume":"384","author":"Mahdavi","year":"2004","journal-title":"Biochem. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1523-5378.2007.00574.x","article-title":"Colonization and infection by Helicobacter pylori in humans","volume":"12","author":"Andersen","year":"2007","journal-title":"Helicobacter"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.2174\/1381612821666150820104028","article-title":"Polysaccharides as Bacterial Antiadhesive Agents and \u201cSmart\u201d Constituents for Improved Drug Delivery Systems against Helicobacter pylori Infection","volume":"21","author":"Menchicchi","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kuo, C.J., Guo, R.T., Lu, I.L., Liu, H.G., Wu, S.Y., Ko, T.P., Wang, A.H.J., and Liang, P.H. (2008). Structure-based inhibitors exhibit differential activities against Helicobacter pylori and Escherichia coli undecaprenyl pyrophosphate synthases. J. Biomed. Biotechnol., 2008.","DOI":"10.1155\/2008\/841312"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1097\/00042737-200212000-00004","article-title":"Levofloxacin based regimens for the eradication of Helicobacter pylori","volume":"14","author":"Zocco","year":"2002","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5669","DOI":"10.3748\/wjg.v18.i40.5669","article-title":"Levofloxacin\/amoxicillin-based schemes vs. quadruple therapy for Helicobacter pylori eradication in second-line","volume":"18","author":"Fini","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"238","DOI":"10.20883\/jms.2016.178","article-title":"A study of ofloxacin and levofloxacin photostability in aqueous solutions","volume":"85","author":"Urbaniak","year":"2016","journal-title":"J. Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-L\u00f3pez, M., Fern\u00e1ndez-Delgado, A., Moy\u00e1, M.L., Blanco-Ar\u00e9valo, D., Carrera, C., de la Haba, R.R., Ventosa, A., Bernal, E., and L\u00f3pez-Cornejo, P. (2019). Optimized preparation of levofloxacin loaded polymeric nanoparticles. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020057"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1038\/s41401-021-00751-z","article-title":"Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization","volume":"42","author":"Chen","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1007\/s00706-015-1482-z","article-title":"Study of inclusion complex of \u03b2-cyclodextrin and levofloxacin and its effect on the solution equilibria between gadolinium(III) ion and levofloxacin","volume":"146","year":"2015","journal-title":"Monatshefte Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.ijbiomac.2017.11.170","article-title":"Formulation and optimization of levofloxacin loaded chitosan nanoparticle for ocular delivery: In-vitro characterization, ocular tolerance and antibacterial activity","volume":"108","author":"Ameeduzzafar","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s10856-015-5658-1","article-title":"Levofloxacin-loaded star poly(\u03b5-caprolactone) scaffolds by additive manufacturing","volume":"27","author":"Puppi","year":"2016","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zheng, H., He, W., Jiao, W., Xia, H., Sun, L., Wang, S., Xiao, J., Ou, X., Zhao, Y., and Shen, A. (2021). Molecular characterization of multidrug-resistant tuberculosis against levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, and delamanid in southwest of China. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06024-8"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fluid.2012.05.027","article-title":"Measurement and correlation for solubility of levofloxacin in six solvents at temperatures from 288.15 to 328.15K","volume":"335","author":"Zhang","year":"2012","journal-title":"Fluid Phase Equilib."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2165\/00003495-200868040-00011","article-title":"Levofloxacin: A review of its use as a high-dose, short-course treatment for bacterial infection","volume":"68","author":"Anderson","year":"2008","journal-title":"Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.1016\/S0032-3861(03)00620-7","article-title":"Synthesis and characterization of biodegradable TPP\/genipin co-crosslinked chitosan gel beads","volume":"44","author":"Mi","year":"2003","journal-title":"Polymer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carbpol.2009.01.016","article-title":"Genipin-crosslinked chitosan hydrogels as biomedical and pharmaceutical aids","volume":"77","author":"Muzzarelli","year":"2009","journal-title":"Carbohydr. Polym."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.carbpol.2016.07.052","article-title":"Injectable and microporous scaffold of densely-packed, growth factor-encapsulating chitosan microgels","volume":"152","author":"Riederer","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.carbpol.2017.06.119","article-title":"Development of carboxymethyl cellulose-chitosan hybrid micro- and macroparticles for encapsulation of probiotic bacteria","volume":"175","author":"Singh","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.jconrel.2004.12.019","article-title":"PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release","volume":"103","author":"Bhattarai","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., Streltsov, D.A., and Ezhov, A.A. (2023). Smart pH- and Temperature-Sensitive Micelles Based on Chitosan Grafted with Fatty Acids to Increase the Efficiency and Selectivity of Doxorubicin and Its Adjuvant Regarding the Tumor Cells. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15041135"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., Ezhov, A.A., Vigovskiy, M.A., Grigorieva, O.A., Dyachkova, U.D., Belogurova, N.G., and Kudryashova, E.V. (2023). Application Prospects of FTIR Spectroscopy and CLSM to Monitor the Drugs Interaction with Bacteria Cells Localized in Macrophages for Diagnosis and Treatment Control of Respiratory Diseases. Diagnostics, 13.","DOI":"10.3390\/diagnostics13040698"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1080\/14786419.2014.918121","article-title":"Does antioxidant properties of the main component of essential oil reflect its antioxidant properties? The comparison of antioxidant properties of essential oils and their main components","volume":"28","author":"Dawidowicz","year":"2014","journal-title":"Nat. Prod. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.foodchem.2015.07.015","article-title":"Practical problems when using ABTS assay to assess the radical-scavenging activity of peptides: Importance of controlling reaction pH and time","volume":"192","author":"Zheng","year":"2016","journal-title":"Food Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0731-7085(98)00150-2","article-title":"The equilibrium constant of \u03b2-cyclodextrin-phenolphtalein complex; Influence of temperature and tetrahydrofuran addition","volume":"18","author":"Zarzycki","year":"1998","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.foodchem.2015.09.052","article-title":"An inclusion complex of eugenol into \u03b2-cyclodextrin: Preparation, and physicochemical and antifungal characterization","volume":"196","author":"Gong","year":"2016","journal-title":"Food Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8156","DOI":"10.1021\/jf402923c","article-title":"Enhanced thermal stability of eugenol by cyclodextrin inclusion complex encapsulated in electrospun polymeric nanofibers","volume":"61","author":"Kayaci","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9729","DOI":"10.1039\/c2cp41092c","article-title":"Correlation of polymer-like solution behaviors with electrospun fiber formation of hydroxypropyl-\u03b2-cyclodextrin and the adsorption study on the fiber","volume":"14","author":"Zhang","year":"2012","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1590\/S1984-82502011000400003","article-title":"Cyclodextrins and ternary complexes: Technology to improve solubility of poorly soluble drugs","volume":"47","author":"Martins","year":"2011","journal-title":"Brazilian J. Pharm. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1006\/jcis.1999.6089","article-title":"Drug\u2014Cyclodextrin Association Constants Determined by Surface Tension and Surface Pressure Measurements","volume":"285","author":"Angelova","year":"1999","journal-title":"J. Colloid Interface Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.molstruc.2018.04.045","article-title":"Equilibrium, structural and antibacterial characterization of moxifloxacin-\u03b2-cyclodextrin complex","volume":"1166","author":"Deme","year":"2018","journal-title":"J. Mol. Struct."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1016\/j.saa.2011.05.084","article-title":"Inclusion of Paracetamol into \u03b2-cyclodextrin nanocavities in solution and in the solid state","volume":"79","author":"Sobhy","year":"2011","journal-title":"Spectrochim. Acta-Part A Mol. Biomol. Spectrosc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.3762\/bjoc.10.241","article-title":"Effect of cyclodextrin complexation on phenylpropanoids\u2019 solubility and antioxidant activity","volume":"10","author":"Kfoury","year":"2014","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Szente, L., Singhal, A., Domokos, A., and Song, B. (2018). Cyclodextrins: Assessing the impact of cavity size, occupancy, and substitutions on cytotoxicity and cholesterol homeostasis. Molecules, 23.","DOI":"10.3390\/molecules23051228"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zlotnikov, I.D., Ezhov, A.A., Ferberg, A.S., Krylov, S.S., Semenova, M.N., Semenov, V.V., and Kudryashova, E.V. (2023). Polymeric Micelles Formulation of Combretastatin Derivatives with Enhanced Solubility, Cytostatic Activity and Selectivity against Cancer Cells. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061613"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Elshafie, H.S., Sakr, S.H., Sadeek, S.A., and Camele, I. (2019). Biological Investigations and Spectroscopic Studies of New Moxifloxacin\/Glycine-Metal Complexes. Chem. Biodivers., 16.","DOI":"10.1002\/cbdv.201800633"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/9\/2353\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:53:47Z","timestamp":1760129627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/9\/2353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,20]]},"references-count":73,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["pharmaceutics15092353"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15092353","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,20]]}}}