{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:33:36Z","timestamp":1792089216987,"version":"4.4.0"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007137","name":"Helse Nord RHF","doi-asserted-by":"publisher","award":["HNF1376-17"],"award-info":[{"award-number":["HNF1376-17"]}],"id":[{"id":"10.13039\/501100007137","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infections and causes serious reproductive tract complications among women. The limitations of existing oral antibiotics and treatment of antimicrobial resistance require alternative treatment options. We are proposing, for the first time, the natural polyphenol resveratrol (RES) in an advanced delivery system comprising liposomes incorporated in chitosan hydrogel, for the localized treatment of C. trachomatis infection. Both free RES and RES liposomes-in-hydrogel inhibited the propagation of C. trachomatis in a concentration-dependent manner, assessed by the commonly used in vitro model comprising McCoy cells. However, for lower concentrations, the anti-chlamydial effect of RES was enhanced when incorporated into a liposomes-in-hydrogel delivery system, with inhibition of 78% and 94% for 1.5 and 3 \u00b5g\/mL RES, respectively for RES liposomes-in-hydrogel, compared to 43% and 72%, respectively, for free RES. Furthermore, RES liposomes-in-hydrogel exhibited strong anti-inflammatory activity in vitro, in a concentration-dependent inhibition of nitric oxide production in the LPS-induced macrophages (RAW 264.7). The combination of a natural substance exhibiting multi-targeted pharmacological properties, and a delivery system that provides enhanced activity as well as applicability for vaginal administration, could be a promising option for the localized treatment of C. trachomatis infection.<\/jats:p>","DOI":"10.3390\/pharmaceutics12121203","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:45:36Z","timestamp":1607906736000},"page":"1203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Liposomes-In-Hydrogel Delivery System Enhances the Potential of Resveratrol in Combating Vaginal Chlamydia Infection"],"prefix":"10.3390","volume":"12","author":[{"given":"May Wenche","family":"J\u00f8raholmen","sequence":"first","affiliation":[{"name":"Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Universitetsveien 57, 9037 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Johannessen","sequence":"additional","affiliation":[{"name":"Research Group for Host Microbe Interactions, Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Universitetsveien 57, 9037 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Gravningen","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infection Control, University Hospital of Northern Norway, Sykehusveien 38, 9019 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7413-6793","authenticated-orcid":false,"given":"Mirja","family":"Puolakkainen","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1997-3107","authenticated-orcid":false,"given":"Ganesh","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital of North Norway, Sykehusveien 38, 9019 Troms\u00f8, Norway"},{"name":"Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8612-9558","authenticated-orcid":false,"given":"Purusotam","family":"Basnet","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital of North Norway, Sykehusveien 38, 9019 Troms\u00f8, Norway"},{"name":"Women\u2019s Health and Perinatology Research Group, Faculty of Health Sciences, UiT The Arctic University of Norway, Universitetsveien 57, 9037 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-2840","authenticated-orcid":false,"given":"Nata\u0161a","family":"\u0160kalko-Basnet","sequence":"additional","affiliation":[{"name":"Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Universitetsveien 57, 9037 Troms\u00f8, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhoea, trichomoniasis and syphilis: Global prevalence and incidence estimates 2016","volume":"97","author":"Rowley","year":"2019","journal-title":"Bull. World Health Organ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.3389\/fcimb.2013.00099","article-title":"Laboratory diagnosis of persistent human chlamydial infection","volume":"3","author":"Puolakkainen","year":"2013","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1473-3099(17)30310-9","article-title":"Sexually transmitted infections: Challenges ahead","volume":"17","author":"Unemo","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.2217\/fmb.10.96","article-title":"Antibiotic resistance in Chlamydiae","volume":"5","author":"Sandoz","year":"2010","journal-title":"Future Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nrmicro3380","article-title":"Molecular mechanisms of antibiotic resistance","volume":"13","author":"Blair","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1177\/0956462415618837","article-title":"2015 European guideline on the management of Chlamydia trachomatis infections","volume":"27","author":"Lanjouw","year":"2016","journal-title":"Int. J. STD AIDS"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"van Dooremalen, W.T.M., Verweij, S.P., den Hartog, J.E., Kebbi-Beghdadi, C., Ouburg, S., Greub, G., Morr\u00e9, S.A., and Ammerdorffer, A. (2020). Screening of Chlamydia trachomatis and Waddlia chondrophila Antibodies in Women with Tubal Factor Infertility. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060918"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"J\u00f8raholmen, M.W., Basnet, P., Tostrup, M.J., Moueffaq, S., and \u0160kalko-Basnet, N. (2019). Localized therapy of vaginal infections and inflammation: Liposomes-in-hydrogel delivery system for polyphenols. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020053"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ijantimicag.2011.02.014","article-title":"Recent advances in understanding the antibacterial properties of flavonoids","volume":"38","author":"Cushnie","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.3390\/molecules20034180","article-title":"Natural products for the treatment of trachoma and Chlamydia trachomatis","volume":"20","author":"Potroz","year":"2015","journal-title":"Molecules"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.ijantimicag.2019.02.015","article-title":"Antibacterial and antifungal properties of resveratrol","volume":"53","author":"Vestergaard","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mattio, L.M., Catinella, G., Dallavalle, S., and Pinto, A. (2020). Stilbenoids: A Natural Arsenal against Bacterial Pathogens. Antibiotics, 9.","DOI":"10.3390\/antibiotics9060336"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Brown, M.A., Potroz, M.G., Teh, S.W., and Cho, N.J. (2016). Natural products for the treatment of chlamydiaceae infections. Microorganisms, 4.","DOI":"10.3390\/microorganisms4040039"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/4064071","article-title":"Resveratrol inhibits propagation of Chlamydia trachomatis in McCoy cells","volume":"2017","author":"Petyaev","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-55975-1","article-title":"Antimicrobial activity of resveratrol-derived monomers and dimers against foodborne pathogens","volume":"9","author":"Mattio","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/ja.2012.43","article-title":"Pre-clinical pharmacokinetics and anti-chlamydial activity of salicylidene acylhydrazide inhibitors of bacterial type III secretion","volume":"65","author":"Slepenkin","year":"2012","journal-title":"J. Antibiot."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zetterstr\u00f6m, C.E., Hasselgren, J., Salin, O., Davis, R.A., Quinn, R.J., Sundin, C., and Elofsson, M. (2013). The resveratrol tetramer (-)-hopeaphenol inhibits type III secretion in the Gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081969"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-1-4939-9694-0_14","article-title":"A Coinfection Model to Evaluate Chlamydia Inc Protein Interactions","volume":"Volume 2042","author":"Brown","year":"2019","journal-title":"Chlamydia Trachomatis: Methods and Protocols"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ejps.2015.09.007","article-title":"Resveratrol-loaded liposomes for topical treatment of the vaginal inflammation and infections","volume":"79","author":"Acharya","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-1-4939-9694-0_16","article-title":"Enumeration of Viable Chlamydia from Infected Animals Using Immunofluorescent Microscopy","volume":"Volume 2042","author":"Brown","year":"2019","journal-title":"Chlamydia Trachomatis: Methods and Protocols"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ejpb.2016.12.029","article-title":"PEGylated liposomes for topical vaginal therapy improve delivery of interferon alpha","volume":"113","author":"Basnet","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ijpharm.2014.06.016","article-title":"Chitosan-coated liposomes for topical vaginal therapy: Assuring localized drug effect","volume":"472","author":"Tho","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3390\/jfb3010037","article-title":"Potentials of chitosan-based delivery systems in wound therapy: Bioadhesion study","volume":"3","author":"Hurler","year":"2012","journal-title":"J. Funct. Biomater."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Korhonen, S., Hokynar, K., Mannonen, L., Paavonen, J., Hiltunen-Back, E., and Puolakkainen, M. (2019). Transcriptional expression of the ompA, cpaf, tarp, and tox genes of Chlamydia trachomatis clinical isolates at different stages of the developmental cycle. Microorganisms, 7.","DOI":"10.3390\/microorganisms7060153"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/jps.22785","article-title":"Liposomal delivery system enhances anti-inflammatory properties of curcumin","volume":"101","author":"Basnet","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ijpharm.2017.12.047","article-title":"Stability, biocompatibility and antioxidant activity of PEG-modified liposomes containing resveratrol","volume":"538","author":"Caddeo","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ejpb.2009.06.006","article-title":"Improvements of cellular stress response on resveratrol in liposomes","volume":"73","author":"Kristl","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jconrel.2018.03.006","article-title":"Transferrin-targeted, resveratrol-loaded liposomes for the treatment of glioblastoma","volume":"277","author":"Jhaveri","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ijantimicag.2018.06.005","article-title":"Resveratrol enhances the efficacy of aminoglycosides against Staphylococcus aureus","volume":"52","author":"Ovsepian","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_30","first-page":"339","article-title":"Characteristics, biological properties and analytical methods of trans-resveratrol: A review","volume":"50","author":"Chorilli","year":"2019","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1517\/17425247.2014.919253","article-title":"Resveratrol: Review on therapeutic potential and recent advances in drug delivery","volume":"11","author":"Pangeni","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.jddst.2019.03.017","article-title":"Drug delivery systems for resveratrol, a non-flavonoid polyphenol: Emerging evidence in last decades","volume":"51","author":"Ahmadi","year":"2019","journal-title":"J. Drug. Deliv. Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.colsurfb.2019.04.030","article-title":"Nanotechnology-based formulations for resveratrol delivery: Effects on resveratrol in vivo bioavailability and bioactivity","volume":"180","author":"Santos","year":"2019","journal-title":"Colloids Surf. B: Biointerfaces"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Intagliata, S., Modica, M.N., Santagati, L.M., and Montenegro, L. (2019). Strategies to improve resveratrol systemic and topical bioavailability: An update. Antioxidants, 8.","DOI":"10.3390\/antiox8080244"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ijpharm.2015.01.003","article-title":"Resveratrol nanoformulations: Challenges and opportunities","volume":"479","author":"Summerlin","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ejpb.2015.04.002","article-title":"Stability and solubility of trans-resveratrol are strongly influenced by pH and temperature","volume":"93","author":"Kristl","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ejps.2013.04.035","article-title":"Nanopharmaceuticals for improved topical vaginal therapy: Can they deliver?","volume":"50","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_38","unstructured":"Chen, Y. (2020). Hydrogels as intrinsic antimicrobials. Hydrogels Based on Natural Polymers, Elsevier BV. [1st ed.]."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1021\/acsinfecdis.8b00138","article-title":"Tiny things with enormous impact: Nanotechnology in the fight against infectious disease","volume":"4","author":"Mitchell","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ijpharm.2008.07.024","article-title":"Effect of resveratrol incorporated in liposomes on proliferation and UV-B protection of cells","volume":"363","author":"Caddeo","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ijpharm.2011.01.056","article-title":"Improving solubility and chemical stability of natural compounds for medicinal use by incorporation into liposomes","volume":"416","author":"Coimbra","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3390\/pharmaceutics5030457","article-title":"Bioavailability of polyphenol liposomes: A challenge ahead","volume":"5","author":"Mignet","year":"2013","journal-title":"Pharmaceutics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1021\/acsinfecdis.9b00232","article-title":"Preserving the efficacy of glycopeptide antibiotics during nanoencapsulation in liposomes","volume":"5","author":"Xu","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_44","first-page":"34","article-title":"Development and in vitro evaluation of a liposomal vaginal delivery system for acyclovir","volume":"1\u20132","author":"Martinac","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5957","DOI":"10.2147\/IJN.S211691","article-title":"Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections","volume":"14","author":"Rukavina","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bonechi, C., Martini, S., Ciani, L., Lamponi, S., Rebmann, H., Rossi, C., and Ristori, S. (2012). Using liposomes as carriers for polyphenolic compounds: The case of trans-resveratrol. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041438"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3109\/08982104.2013.826242","article-title":"Novel vaginal drug delivery system: Deformable propylene glycol liposomes-in-hydrogel","volume":"24","author":"Hurler","year":"2014","journal-title":"J. Liposome Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"J\u00f8raholmen, M.W., Bhargava, A., Julin, K., Johannessen, M., and \u0160kalko-Basnet, N. (2020). The antimicrobial properties of chitosan can be tailored by formulation. Mar. Drugs, 18.","DOI":"10.3390\/md18020096"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijpharm.2013.08.033","article-title":"The effect of lipid composition and liposome size on the release properties of liposomes-in-hydrogel","volume":"456","author":"Hurler","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Leyva-G\u00f3mez, G., Del Prado-Audelo, M.L., Ortega-Pe\u00f1a, S., Mendoza-Mu\u00f1oz, N., Urb\u00e1n-Morl\u00e1n, Z., Gonz\u00e1lez-Torres, M., Gonz\u00e1lez-Del Carmen, M., Figueroa-Gonz\u00e1lez, G., Reyes-Hern\u00e1ndez, O.D., and Cort\u00e9s, H. (2019). Modifications in Vaginal Microbiota and Their Influence on Drug Release: Challenges and Opportunities. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11050217"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"119867","DOI":"10.1016\/j.ijpharm.2020.119867","article-title":"Recent advances in hydrogels as strategy for drug delivery intended to vaginal infections","volume":"590","author":"Carvalho","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10029","DOI":"10.1038\/srep10029","article-title":"Resveratrol antibacterial activity against Escherichia coli is mediated by Z-ring formation inhibition via suppression of FtsZ expression","volume":"5","author":"Hwang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1007\/s11274-010-0325-7","article-title":"Antimicrobial activity and effects of resveratrol on human pathogenic bacteria","volume":"26","author":"Paulo","year":"2010","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-58872-0","article-title":"Exploring resveratrol dimers as virulence blocking agents\u2013Attenuation of type III secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa","volume":"10","author":"Sundin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Giordani, B., Basnet, P., Mishchenko, E., Luppi, B., and \u0160kalko-Basnet, N. (2020). Utilizing liposomal quercetin and gallic acid in localized treatment of vaginal candida infections. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010009"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1021\/acsinfecdis.5b00116","article-title":"Nanomaterials for the treatment of bacterial biofilms","volume":"2","author":"Wang","year":"2016","journal-title":"ACS Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1002\/jps.23571","article-title":"Ability of chitosan gels to disrupt bacterial biofilms and their applications in the treatment of bacterial vaginosis","volume":"102","author":"Kandimalla","year":"2013","journal-title":"J. Pharm. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"647","DOI":"10.4155\/fmc.15.7","article-title":"Agents that inhibit bacterial biofilm formation","volume":"7","author":"Rabin","year":"2015","journal-title":"Future Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"390","DOI":"10.15698\/mic2016.09.525","article-title":"Chlamydia trachomatis genital infections","volume":"3","author":"Ferone","year":"2016","journal-title":"Microb. Cell"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/12\/1203\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:43:50Z","timestamp":1760179430000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/12\/1203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,11]]},"references-count":59,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["pharmaceutics12121203"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12121203","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,11]]}}}