{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:01:13Z","timestamp":1765886473836,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology (FCT), Portugal","doi-asserted-by":"publisher","award":["SFRH\/BDE\/112920\/2015"],"award-info":[{"award-number":["SFRH\/BDE\/112920\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Cytolytic vaginosis or, classically, Doderlein\u2019s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w\/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm\/kg (F4) and 1065 mOsm\/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v\/v) in terms of dilution. Additionally, the 4% (w\/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2\/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v\/v) dilution. Conclusions: Based on these results, the 4% (w\/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application.<\/jats:p>","DOI":"10.3390\/pharmaceutics16111436","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"1436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0144-2543","authenticated-orcid":false,"given":"Carlos","family":"Gaspar","sequence":"first","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Labfit\u2014HPRD Health Products Research and Development, Lda, Edif\u00edcio UBIMEDICAL Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1031-329X","authenticated-orcid":false,"given":"Ana Sofia","family":"Agonia","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Labfit\u2014HPRD Health Products Research and Development, Lda, Edif\u00edcio UBIMEDICAL Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"given":"Sara","family":"Fel\u00edcio","sequence":"additional","affiliation":[{"name":"Labfit\u2014HPRD Health Products Research and Development, Lda, Edif\u00edcio UBIMEDICAL Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"given":"Mariana","family":"Tom\u00e1s","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"}]},{"given":"Diana","family":"Esteves","sequence":"additional","affiliation":[{"name":"Labfit\u2014HPRD Health Products Research and Development, Lda, Edif\u00edcio UBIMEDICAL Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9311-8355","authenticated-orcid":false,"given":"Rita","family":"Palmeira-de-Oliveira","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Labfit\u2014HPRD Health Products Research and Development, Lda, Edif\u00edcio UBIMEDICAL Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-6254","authenticated-orcid":false,"given":"Gilbert G. G.","family":"Donders","sequence":"additional","affiliation":[{"name":"Femicare Clinical Research for Women, 3300 Tienen, Belgium"},{"name":"Department of Obstetrics and Gynecology, University of Antwerp, 2550 Edegem, Belgium"},{"name":"Department of Obstetrics and Gynecology, Regional Hospital, 3300 Tienen, Belgium"}]},{"given":"Jos\u00e9","family":"Martinez-de-Oliveira","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"}]},{"given":"Ana","family":"Palmeira-de-Oliveira","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilh\u00e3, Portugal"},{"name":"Labfit\u2014HPRD Health Products Research and Development, Lda, Edif\u00edcio UBIMEDICAL Estrada Municipal 506, 6200-284 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/S0002-9378(12)90736-X","article-title":"Cytolytic Vaginosis","volume":"165","author":"Cibley","year":"1991","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.4103\/0253-7184.55490","article-title":"Cytolytic Vaginosis: A Review","volume":"30","author":"Suresh","year":"2009","journal-title":"Indian J. Sex. Transm. Dis. AIDS"},{"key":"ref_3","unstructured":"Bergey, D.H. (2009). Bergey\u2019s Manual of Systematic Bacteriology\u2014Volume3: The Firmicutes, Springer."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1099\/ijsem.0.004107","article-title":"A Taxonomic Note on the Genus Lactobacillus: Description of 23 Novel Genera, Emended Description of the Genus Lactobacillus Beijerinck 1901, and Union of Lactobacillaceae and Leuconostocaceae","volume":"70","author":"Zheng","year":"2020","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e22653","DOI":"10.1002\/jcla.22653","article-title":"Characterization of the Vaginal Microbiome during Cytolytic Vaginosis Using High-Throughput Sequencing","volume":"33","author":"Xu","year":"2019","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1097\/LGT.0000000000000565","article-title":"Variation of the Vaginal Lactobacillus Microbiome in Cytolytic Vaginosis","volume":"24","author":"Yang","year":"2020","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1128\/JCM.40.8.2746-2749.2002","article-title":"Vaginal Lactobacillus Flora of Healthy Swedish Women","volume":"40","author":"Jakobsson","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_8","first-page":"652","article-title":"Spectrum of Lactobacillus Species Present in Healthy Vagina of Indian Women","volume":"129","author":"Garg","year":"2009","journal-title":"Indian J. Med. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12934-020-01464-4","article-title":"Vaginal Microbiota and the Potential of Lactobacillus Derivatives in Maintaining Vaginal Health","volume":"19","author":"Chee","year":"2020","journal-title":"Microb. Cell Fact."},{"key":"ref_10","first-page":"21","article-title":"The Occurrence of Bacillus Vaginalis D\u00f6derlein and Cytolysis in Dysplasia, Carcinoma in Situ, and Invasive Carcinoma of the Uterine Cervix","volume":"16","author":"Nasielli","year":"1972","journal-title":"Acta Cytol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kraut, R., Carvallo, F.D., Golonka, R., Campbell, S.M., Rehmani, A., Babenko, O., Lee, M.-C., and Vieira-Baptista, P. (2023). Scoping Review of Cytolytic Vaginosis Literature. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0280954"},{"key":"ref_12","first-page":"23","article-title":"Cytolytic Vaginosis: Examination of 2947 Vaginal Smears","volume":"11","author":"Demirezen","year":"2003","journal-title":"Cent. Eur. J. Public Health"},{"key":"ref_13","first-page":"106","article-title":"Cytolytic Vaginosis: An Underdiagnosed Pathology That Mimics Vulvovaginal Candidiasis","volume":"11","author":"Soares","year":"2017","journal-title":"Acta Obs. Ginecol. Port."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1745-7599.2000.tb00284.x","article-title":"Pearls for Practice. Cytolytic Vaginosis: An Overlooked Cause of Cyclic Vaginal Itching and Burning","volume":"12","author":"Hutti","year":"2000","journal-title":"J. Am. Acad. Nurse Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105621","DOI":"10.1016\/j.ejps.2020.105621","article-title":"Sodium Bicarbonate Gels: A New Promising Strategy for the Treatment of Vulvovaginal Candidosis","volume":"157","author":"Rolo","year":"2021","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_16","first-page":"627673","article-title":"Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis","volume":"2014","year":"2014","journal-title":"Sci. World J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.4239\/wjd.v9.i11.199","article-title":"Use of Sodium Bicarbonate and Blood Gas Monitoring in Diabetic Ketoacidosis: A Review","volume":"9","author":"Patel","year":"2018","journal-title":"World J. Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jcrc.2019.02.027","article-title":"Sodium Bicarbonate Therapy for Critically Ill Patients with Metabolic Acidosis: A Scoping and a Systematic Review","volume":"51","author":"Fujii","year":"2019","journal-title":"J. Crit. Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.semnephrol.2019.06.007","article-title":"Managing Chloride and Bicarbonate in the Prevention and Treatment of Acute Kidney Injury","volume":"39","author":"Haines","year":"2019","journal-title":"Semin. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cvsm.2016.09.005","article-title":"Is Bicarbonate Therapy Useful?","volume":"47","author":"Hopper","year":"2017","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"259","DOI":"10.3109\/13625187.2014.980501","article-title":"Women\u2019s Experiences, Preferences and Perceptions Regarding Vaginal Products: Results from a Cross-Sectional Web-Based Survey in Portugal","volume":"20","author":"Duarte","year":"2015","journal-title":"Eur. J. Contracept. Reprod. Health Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114133","DOI":"10.1016\/j.addr.2022.114133","article-title":"Women\u2019s Preferences and Acceptance for Different Drug Delivery Routes and Products","volume":"182","author":"Oliveira","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Adeva-Andany, M.M., Carneiro-Freire, N., Donapetry-Garc\u00eda, C., Ra\u00f1al-Mu\u00ed\u00f1o, E., and L\u00f3pez-Pereiro, Y. (2014). The Importance of the Ionic Product for Water to Understand the Physiology of the Acid-Base Balance in Humans. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/695281"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0010-7824(99)00010-4","article-title":"A Vaginal Fluid Simulant","volume":"59","author":"Owen","year":"1999","journal-title":"Contraception"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.ejpb.2007.12.007","article-title":"Performance of an in Vitro Mucoadhesion Testing Method for Vaginal Semisolids: Influence of Different Testing Conditions and Instrumental Parameters","volume":"69","author":"Amaral","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/OLQ.0b013e3181644669","article-title":"Mucosal Irritation Potential of Personal Lubricants Relates to Product Osmolality as Detected by the Slug Mucosal Irritation Assay","volume":"35","author":"Adriaens","year":"2008","journal-title":"Sex. Transm. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3390\/pharmaceutics6030530","article-title":"Characterization of Commercially Available Vaginal Lubricants: A Safety Perspective","volume":"6","author":"Cunha","year":"2014","journal-title":"Pharmaceutics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.ejps.2017.09.009","article-title":"Vaginal Semisolid Products: Technological Performance Considering Physiologic Parameters","volume":"109","author":"Machado","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_29","unstructured":"Prista, L.V.N., Alves, A.C., and Morgado, R. (1996). Tecnologia Farmac\u00eautica, Servi\u00e7o de Educa\u00e7\u00e3o e Bolsas. [4th ed.]. Funda\u00e7\u00e3o Calouste Gulbenkian."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ijpharm.2006.07.036","article-title":"Evaluation of the Physical Stability of Two Oleogels","volume":"327","author":"Almeida","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_31","unstructured":"EMA (2003). Note For Guidance On Evaluation Of Stability Data (CPMP\/ICH\/420\/02), EMA."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.anaerobe.2019.06.004","article-title":"Development and Validation of a New One Step Multiplex-PCR Assay for the Detection of Ten Lactobacillus Species","volume":"59","author":"Gaspar","year":"2019","journal-title":"Anaerobe"},{"key":"ref_33","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (2022). Broth Microdilution\u2014EUCAST Reading Guide, The European Committee on Antimicrobial Susceptibility Testing. Version 4.0."},{"key":"ref_34","unstructured":"(2009). Biological Evaluation of Medical Devices: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5)."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1016\/j.xphs.2019.05.026","article-title":"Optimization and Application of In Vitro and Ex Vivo Models for Vaginal Semisolids Safety Evaluation","volume":"108","author":"Machado","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_36","first-page":"14","article-title":"Compendium of Pharmaceutical Excipients for Vaginal Formulations","volume":"25","author":"Garg","year":"2001","journal-title":"Pharm. Technol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/j.addr.2005.07.004","article-title":"The Use of Mucoadhesive Polymers in Vaginal Delivery","volume":"57","author":"Valenta","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1081\/DDC-100105179","article-title":"Development of a Mucoadhesive Dosage Form for Vaginal Administration","volume":"27","author":"Ceschel","year":"2001","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_39","unstructured":"World Health Organization (2011). Advisory Note Use and Procurement of Additional Lubricants for Male and Female Condoms: WHO\/UNFPA\/FHI360 Advisory Note, World Health Organization."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2006.03.012","article-title":"Gels as Vaginal Drug Delivery Systems","volume":"318","author":"Bahia","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"543","DOI":"10.3390\/pharmaceutics6040543","article-title":"What Do Portuguese Women Prefer Regarding Vaginal Products? Results from a Cross-Sectional Web-Based Survey","volume":"6","author":"Duarte","year":"2014","journal-title":"Pharmaceutics"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Matare, T., Nziramasanga, P., Gwanzura, L., and Robertson, V. (2017). Experimental Germ Tube Induction in Candida Albicans: An Evaluation of the Effect of Sodium Bicarbonate on Morphogenesis and Comparison with Pooled Human Serum. BioMed Res. Int., 2017.","DOI":"10.1155\/2017\/1976273"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.prosdent.2017.12.022","article-title":"Chemical Hygiene Protocols for Complete Dentures: A Crossover Randomized Clinical Trial","volume":"121","author":"Maske","year":"2019","journal-title":"J. Prosthet. Dent."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00284-014-0585-9","article-title":"Formic Acid and Acetic Acid Induce a Programmed Cell Death in Pathogenic Candida Species","volume":"69","author":"Lastauskien","year":"2014","journal-title":"Curr. Microbiol."},{"key":"ref_45","unstructured":"Rowe, R.C., Sheskey, P.J., and Quinn, M.E. (2009). Handbook of Pharmaceutical Excipients, Pharmaceutical Press and the American Pharmacists Association. [6th ed.]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ejpb.2010.07.004","article-title":"Formulation of Mucoadhesive Vaginal Hydrogels Insensitive to Dilution with Vaginal Fluids","volume":"76","author":"Bouchemal","year":"2010","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors","volume":"12","author":"Edmondson","year":"2014","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/BF02634339","article-title":"Effects of Methylcellulose on Epithelial Cells","volume":"29","author":"Gallik","year":"1993","journal-title":"Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1111\/jam.12947","article-title":"In Vitro Evaluation on HeLa Cells of Protective Mechanisms of Probiotic Lactobacilli against Candida Clinical Isolates","volume":"119","author":"Coman","year":"2015","journal-title":"J. Appl. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"He, Y., Niu, X., Wang, B., Na, R., Xiao, B., and Yang, H. (2020). Evaluation of the Inhibitory Effects of Lactobacillus Gasseri and Lactobacillus Crispatus on the Adhesion of Seven Common Lower Genital Tract Infection-Causing Pathogens to Vaginal Epithelial Cells. Front. Med., 7.","DOI":"10.3389\/fmed.2020.00284"},{"key":"ref_51","first-page":"1103","article-title":"Report: Synergism of Sodium Bicarbonate and Baicalin against Clinical Candida Albicans Isolates via Broth Microdilution Method and Checkerboard Assay","volume":"32","author":"Shao","year":"2019","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1590\/S1806-83242009000400006","article-title":"Effect of Sodium Bicarbonate on Candida Albicans Adherence to Thermally Activated Acrylic Resin","volume":"23","author":"Paradella","year":"2009","journal-title":"Braz. Oral Res."},{"key":"ref_53","first-page":"206","article-title":"Cytolytic Vaginosis: A Brief Review","volume":"1","author":"Varma","year":"2022","journal-title":"J. Ski. Sex. Transm. Dis."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/11\/1436\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:29:54Z","timestamp":1760113794000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/11\/1436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":53,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["pharmaceutics16111436"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16111436","relation":{},"ISSN":["1999-4923"],"issn-type":[{"type":"electronic","value":"1999-4923"}],"subject":[],"published":{"date-parts":[[2024,11,11]]}}}