Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis
<b>Background/Objectives:</b> Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the <i>Lactobacillus</i> genus, which leads to high amounts of lactic acid in the vaginal environment. <i>Lactobacillus crispatu...
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| author | Carlos Gaspar Ana Sofia Agonia Sara Felício Mariana Tomás Diana Esteves Rita Palmeira-de-Oliveira Gilbert G. G. Donders José Martinez-de-Oliveira Ana Palmeira-de-Oliveira |
| author_facet | Carlos Gaspar Ana Sofia Agonia Sara Felício Mariana Tomás Diana Esteves Rita Palmeira-de-Oliveira Gilbert G. G. Donders José Martinez-de-Oliveira Ana Palmeira-de-Oliveira |
| author_sort | Carlos Gaspar |
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| description | <b>Background/Objectives:</b> Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the <i>Lactobacillus</i> genus, which leads to high amounts of lactic acid in the vaginal environment. <i>Lactobacillus crispatus</i> 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. <b>Methods:</b> In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (<i>w/w</i>). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. <b>Results:</b> 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 <i>L. crispatus</i> strains, with MIC values ranging from 6.25% to 25% (<i>v/v</i>) in terms of dilution. Additionally, the 4% (<i>w/w</i>) gel significantly interfered with the adhesion of <i>L. crispatus</i> 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% (<i>v/v</i>) dilution. <b>Conclusions</b>: Based on these results, the 4% (<i>w/w</i>) 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. |
| format | Article |
| id | doaj-art-1519b0953fe0442fac59488020c876a5 |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
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| spelling | doaj-art-1519b0953fe0442fac59488020c876a52025-08-20T02:48:07ZengMDPI AGPharmaceutics1999-49232024-11-011611143610.3390/pharmaceutics16111436Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic VaginosisCarlos Gaspar0Ana Sofia Agonia1Sara Felício2Mariana Tomás3Diana Esteves4Rita Palmeira-de-Oliveira5Gilbert G. G. Donders6José Martinez-de-Oliveira7Ana Palmeira-de-Oliveira8CICS-UBI—Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilhã, PortugalCICS-UBI—Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilhã, PortugalLabfit—HPRD Health Products Research and Development, Lda, Edifício UBIMEDICAL Estrada Municipal 506, 6200-284 Covilhã, PortugalCICS-UBI—Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilhã, PortugalLabfit—HPRD Health Products Research and Development, Lda, Edifício UBIMEDICAL Estrada Municipal 506, 6200-284 Covilhã, PortugalCICS-UBI—Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilhã, PortugalFemicare Clinical Research for Women, 3300 Tienen, BelgiumCICS-UBI—Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilhã, PortugalCICS-UBI—Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-358 Covilhã, Portugal<b>Background/Objectives:</b> Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the <i>Lactobacillus</i> genus, which leads to high amounts of lactic acid in the vaginal environment. <i>Lactobacillus crispatus</i> 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. <b>Methods:</b> In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (<i>w/w</i>). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. <b>Results:</b> 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 <i>L. crispatus</i> strains, with MIC values ranging from 6.25% to 25% (<i>v/v</i>) in terms of dilution. Additionally, the 4% (<i>w/w</i>) gel significantly interfered with the adhesion of <i>L. crispatus</i> 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% (<i>v/v</i>) dilution. <b>Conclusions</b>: Based on these results, the 4% (<i>w/w</i>) 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.https://www.mdpi.com/1999-4923/16/11/1436cytolytic vaginosis<i>Lactobacillus</i>sodium bicarbonatevaginagels |
| spellingShingle | Carlos Gaspar Ana Sofia Agonia Sara Felício Mariana Tomás Diana Esteves Rita Palmeira-de-Oliveira Gilbert G. G. Donders José Martinez-de-Oliveira Ana Palmeira-de-Oliveira Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis Pharmaceutics cytolytic vaginosis <i>Lactobacillus</i> sodium bicarbonate vagina gels |
| title | Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis |
| title_full | Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis |
| title_fullStr | Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis |
| title_full_unstemmed | Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis |
| title_short | Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis |
| title_sort | development and characterization of sodium bicarbonate based gel for cytolytic vaginosis |
| topic | cytolytic vaginosis <i>Lactobacillus</i> sodium bicarbonate vagina gels |
| url | https://www.mdpi.com/1999-4923/16/11/1436 |
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