Vaginal Products Research Articles

Prasterone (Intrarosa)


 CADTH recommends that Intrarosa should be reimbursed by public drug plans for the treatment of postmenopausal vulvovaginal atrophy (VVA) if certain conditions are met.
 Intrarosa should only be covered for patients who are eligible for vaginal estrogen products that are currently reimbursed by public drug plans for the treatment of postmenopausal VVA.
 Intrarosa should only be reimbursed if treatment with Intrarosa does not cost more than treatment with the least costly vaginal estrogen product currently reimbursed for the treatment of postmenopausal VVA.

Preliminary Data from Clinical Trial to Survey Results of Flourish Vaginal Care System for Recurrent BV [A80

INTRODUCTION: Bacterial vaginosis (BV) is a vaginal dysbiosis causing pain, irritation, discharge, odor, and itching. Antibiotic treatment is standard of care, but BV recurs in up to 50% of patients in 1 year. We hypothesized that using the Flourish Vaginal Care (FVC) system (an over-the-counter kit by Good Clean Love), with iso-osmotic components to optimize vaginal pH and Lactobacillus levels would reduce BV recurrence. METHODS: Ten women with two or more BV episodes within the past 2 years were enrolled in the pilot study for 11 weeks. Participants were treated with metronidazole and simultaneously started on a daily external wash with pH<4.4; iso-osmolar intravaginal lactic acid-containing gel every other day, and vaginal homeopathic suppository in a probiotic base every 3 days. Outcomes were vaginal pH, BV, and yeast occurrence tested biweekly. Participants journaled associated symptoms daily. Patient satisfaction was determined via telephone interview 10-12 months post trial. RESULTS: During the trial, no participants had BV recurrence. Mean vaginal pH decreased from 4.54 to 4.08 at baseline to study end. Journals showed decreased frequencies of pain and irritation (∼2-fold) and itching (∼4-fold). All (100%) of subjects participating in telephone interviews were satisfied with their symptom resolution 10-12 months post trial. CONCLUSION: Our pilot study shows that consistent use of vaginal products that are iso-osmotic and support optimal vaginal pH with bio-matched lactic acid prevents BV recurrence and alleviates associated symptoms. This work has important implications for prevention of recurrent BV and is evidence for the importance of maintaining the vaginal microbiome.

Correlates of non-persistent endocrine disrupting chemical mixtures among reproductive-aged Black women in Detroit, Michigan

Some studies indicate that Black women have higher exposure to multiple non-persistent endocrine disrupting chemicals (EDCs) than white women, but little is known about correlates of exposure to EDC mixtures. Using baseline data from a prospective cohort study of reproductive-aged Black women (N = 751), we characterized profiles of EDC mixtures and identified correlates of exposure. At baseline, we quantified biomarkers of 16 phthalates, 7 phenols, 4 parabens, and triclocarban in urine and collected covariate data through self-administered questionnaires and interviews. We used principal component (PC) analysis and k-means clustering to describe EDC mixture profiles. Associations between correlates and PCs were estimated as the mean difference (β) in PC scores, while associations between correlates and cluster membership were estimated as the odds ratio (OR) of cluster membership. Personal care product use was consistently associated with profiles of higher biomarker concentrations of non-persistent EDCs. Use of nail polish, menstrual and vaginal products (e.g., vaginal powder, vaginal deodorant), and sunscreen was associated with a mixture of phthalate and some phenol biomarkers using both methods. Current vaginal ring use, a form of hormonal contraception placed inside the vagina, was strongly associated with higher concentrations of high molecular weight phthalate biomarkers (k-means clustering: OR = 2.42, 95% CI = 1.28, 4.59; PCA: β = −0.32, 95% CI = −0.71, 0.07). Several dietary, reproductive, and demographic correlates were also associated with mixtures of EDC biomarkers. These findings suggest that personal care product use, diet, and contraceptive use may be sources of exposure to multiple non-persistent EDCs among reproductive-aged Black women. Targeted interventions to reduce exposure to multiple EDCs among Black women are warranted.

Burch Procedure: A Historical Perspective.

The Burch procedure (1961) was considered the gold standard treatment for stress urinary incontinence (SUI) before the midurethral slings (MUSs) were introduced, in 2001. This historical perspective of the Burch's timeline can encourage urogynecological surgeons to master the Burch technique as one of the options for surgical treatment of SUI. A bibliographic search was performed in the PubMed and National Library of Medicine (NIH) databases with the terms Burch colposuspension AND history AND stress urinary incontinence in the last 20 years. The original article by Burch (1961) was included. The references were read by three authors. The exclusion criterion was studies in non-English languages. Biomedical Library Special Collections were included as historical relevant search. Some modifications of the technique have been made since the Burch procedure was first described. The interest in this technique has been increasing due to the negative publicity associated with vaginal synthetic mesh products. Twenty-nine relevant articles were included in the present review article, and numerous trials have compared Burch colposuspension with MUS. This historical perspective enables the scientific community to review a standardized technique for SUI. Burch colposuspension should be considered an appropriate surgical treatment for women with SUI, and an option in urogynecological training programs worldwide.

Estradiol (Imvexxy)


 CADTH recommends that Imvexxy be reimbursed by public drug plans for the treatment of moderate-to-severe dyspareunia (painful sex) in women who are postmenopausal if certain conditions are met.
 Imvexxy should only be covered in a similar manner as other vaginal estrogen products that include treatment of women who are postmenopausal and have moderate-to-severe painful sex.
 Imvexxy should only be reimbursed if it is cost saving for drug programs compared to the least costly local hormone therapy reimbursed for the treatment of moderate-to-severe painful sex, a symptom of vulvar and vaginal atrophy (VVA) in women who are postmenopausal.

Recent Advances in the Excipients Used in Modified Release Vaginal Formulations.

The formulation of an ideal vaginal drug delivery system (DDS), with the requisite properties, with respect to safety, efficacy, patient compliance, aesthetics, harmonization with the regulatory requirements, and cost, requires a meticulous selection of the active ingredients and the excipients used. Novel excipients defined by diversity and multifunctionality are used in order to ameliorate drug delivery attributes. Synthetic and natural polymers are broadly used in pharmaceutical vaginal formulations (solid, semi-solid dosage forms, implantable devices, and nanomedicines) with a promising perspective in improving stability and compatibility issues when administered topically or systemically. Moreover, the use of biopolymers is aiming towards formulating novel bioactive, biocompatible, and biodegradable DDSs with a controllable drug release rate. Overviewing vaginal microenvironment, which is described by variable and perplexed features, a perceptive choice of excipients is essential. This review summarizes the recent advances on the excipients used in modified vaginal drug delivery formulations, in an attempt to aid the formulation scientist in selecting the optimal excipients for the preparation of vaginal products.

Development of Gram Stain Scoring System Based on Pro-Inflammatory Cytokines in the Sheep Model for Testing Toxicity of Vaginal Products.

Background: Development of safe, effective products to prevent the sexual transmission of HIV remains a priority. Prior to clinical testing, the products must undergo strict safety evaluations to avoid mucosal drug toxicity, inflammation, and vaginal microbiome (VMB) shifts. Based on the Food and Drug Administration (FDA) guidance, we designed a study to measure the inflammatory markers and VMB changes after intravaginal treatment with products that have been associated with toxicity, with the objective to develop a Gram stain slide scoring system, similar to Nugent scoring, correlated with the proinflammatory cytokines in sheep.Methods: Non-pregnant Dorset ewes (n = 34) were randomized to receive 5 ml intravaginal 4% nonoxynol-9 (N9) contraceptive gel, positive control (0.2% benzalkonium chloride), placebo control [hydroxethyl cellulose (HEC)], or no application daily for 10 days, with 11-day post-treatment follow-up. The vaginal swabs were collected for the cytokines, VMB, and Gram-stained slides. An enzyme-linked immunosorbent assay (ELISA) analysis of cytokines interleukin (IL)-1β, IL-8, CXCL10, and tumor necrosis factor-α (TNF-α) was used to determine inflammatory state of the sample. Vaginal microbiome community types (CT) were utilized to create five equivalent slide subsets for iterative development of a Gram-stained slide scoring system with comparisons with inflammatory state based on the cytokine levels.Results: Digital images of the Gram-stained slides were scored based on Gram staining and morphology of bacteria, presence of sheep epithelial cells, and immune cells. The scoring system was modified in an iterative fashion with weighting based on cytokine categorization of inflamed samples, with three of four cytokine values above the mean indicating that the sample was inflamed. The parameters in the final version of the scoring system included mature epithelial cells, Gram-negative rods, and Gram-positive diplococci indicating normal and immune cells indicating inflammation. The area under the receiver operator characteristic curve (ROC AUC) was 0.725 (ROC AUCs range between 0.5 and 1.0) with a greater area indicating higher diagnostic ability of a test with a binary outcome: inflamed or normal.Conclusion: The scoring system, derived from the advanced VMB and cytokine analyses, provides a validated, practical method for quantification of Gram-stained slides that can be performed in most laboratories, increasing the potential for standardization. The training plan can assist laboratories to determine the safety of intravaginal products in their sheep studies or the methodological approach can be applied to other animal models where such data are also needed.

Impact of vaginal douching products on vaginal Lactobacillus, Escherichia coli and epithelial immune responses

We compared the effect of commercial vaginal douching products on Lactobacillus crispatus, L. jensenii, L. gasseri, L. iners, E. coli, and immortalized vaginal epithelial cells (VK2). All studied douching products (vinegar, iodine and baking soda based) induced epithelial cell death, and all inhibited growth of E. coli. Co-culture of vaginal epithelial cells with any of the lactobacilli immediately following exposure to douching products resulted in a trend to less human cell death. However, co-culture of epithelial cells with L. iners was associated with higher production of IL6 and IL8, and lower IL1RA regardless of presence or type of douching solution. Co-culture with L. crispatus or L. jensenii decreased IL6 production in the absence of douches, but increased IL6 production after exposure to vinegar. Douching products may be associated with epithelial disruption and inflammation, and may reduce the anti-inflammatory effects of beneficial lactobacilli.

Vaginal pH Value for Clinical Diagnosis and Treatment of Common Vaginitis.

In modern society, 75% of all women worldwide have had vaginitis at least once in their lives. The vagina has a dynamic microbial ecosystem with varying vaginal pH levels. An imbalance in that ecosystem can alter the vaginal pH and tip the scale to the point of causing issues, such as vaginitis, that require medical attention. Although vaginitis is not an incurable disease, it causes discomfort and pain that disrupt women’s daily lives. The most common causes of vaginitis include bacterial vaginosis, trichomoniasis, and vulvovaginal candidiasis. In this review, we discuss the causes, diagnostic methods, and symptoms of different types of vaginitis, the relationship of vaginitis to the prevalence of other diseases, issues associated with recurrent vaginitis and the immune system, and a variety of effective available treatments. In our article, we summarize the relationship of pH with the vaginal ecosystem, discuss the associated factors of vaginal pH, and finally introduce the different available vaginal pH self-test products.

The role of topic vaginal products as part of the therapeutic strategy in uterine cervix lesions

It has been widely demonstrated so far that lactobacilli represent probably the most important microorganisms which are developed at the level of the vaginal cavity and which are responsible for the maintenance of an adequate environment and pH at this level. Once the number of these microorganisms decrease the pH value increase leading to the apparition of a basic medium, which favors the development of certain microorganisms such as human papilloma virus. Meanwhile it is widely known that the presence of this virus is associated with an increased risk of developing premalignant and even malignant conditions. The aim of the current paper is to investigate the correlation between the vaginal pH, the risk of human papilloma virus infection and, in the meantime, to explore the possible benefits of local application of Cerviron, a topic, vaginal product which seems to significantly influence the risk of cervical lesions development.

The role of topic vaginal products in posthysterectomy vaginal atrophy

Vaginal atrophy represents a frequently encountered condition which is significantly correlated with decreased amounts of circulating oestrogen levels. It is usually characterized by the presence of burning, itching, irritation and dyspareunia. In such cases attention was focused on identifying a topic product which might alleviate these symptoms and stop the deterioration process of the vaginal lining. One product which seems to have an effective role in order to stop this process and to offer a good local control of the disease should contain anti-inflammatory, healing and antiseptic principles. The aim of the current paper is to study the possible benefits of Cerviron a topic product with intravaginal administration which contains seven active principles in order to offer the above mentioned effects.

Factors Associated with Vaginal Lactobacillus Predominance Among African American Women Early in Pregnancy.

Background: Vaginal Lactobacillus is considered protective of some adverse reproductive health outcomes, including preterm birth. However, factors that increase or decrease the likelihood of harboring Lactobacillus in the vaginal microbiome remain largely unknown. In this study, we sought to identify risk and protective factors associated with vaginal Lactobacillus predominance within a cohort of pregnant African American women. Materials and Methods: Vaginal microbiome samples were self-collected by African American women (N = 436) during their 8-14th week of pregnancy. Sociodemographic information and measures of health behaviors, including substance use, antibiotic exposure, sexual practices, frequency of vaginal intercourse, and the use of vaginal products, were collected through participant self-report. The V3-V4 region of the 16S rRNA gene was targeted for amplification and sequencing using Illumina HiSeq, with bacterial taxonomy assigned using the PECAN classifier. Univariate and a series of multivariate logistic regression models identified factors predictive of diverse vaginal microbiota or Lactobacillus predominance. Results: Participants who used marijuana in the past 30 days (aOR 1.80, 95% CI 1.08-2.98) were more likely to have diverse non-Lactobacillus-predominant vaginal microbiota, as were women not living with their partners (aOR 1.90, 95% CI 1.20-3.01). Cohabitating or marijuana usage were not associated with type of Lactobacillus (non-iners Lactobacillus vs. Lactobacillus iners) predominance (aOR 1.11, 95% CI 0.52-2.38 and aOR 0.56, 95% CI 0.21-1.47, respectively). Conclusions: Living with a partner is conducive to vaginal Lactobacillus predominance. As such, cohabitation may be in important covariate to consider in vaginal microbiome studies.

The Environmental Injustice of Beauty: an intersectional analysis of vaginal care products by race/ethnicity and socioeconomic status

BACKGROUND AND AIM: The environmental injustice of beauty framework links intersectional systems of oppression (e.g. racism, sexism, classism) to racialized beauty practices and poor health outcomes. Historical and ongoing discrimination around vaginal odors especially among women of color can influence menstrual and other vaginal product use, which are a source of exposure to harmful chemical mixtures. The aim of this analysis is to examine differences in vaginal product use by race/ethnicity and socioeconomic status. METHODS: We combined survey data on vaginal product use from the following two studies focused on the health of Black and Latina reproductive-aged women: a hospital-based study in the Washington, DC area (FORGE) and a community-based study in California (Taking Stock). Vaginal product use was examined at the intersections of race/ethnicity (Black (N=185), Latina (N=156), White (N=71), and Other (N=84) and socioeconomic status (≦High School (HS) education (N=99) versus HS (N=391)). RESULTS:Significant differences exist in the type of vaginal care products used by racial/ethnicity as well as by educational attainment. Tampon and menstrual cup use were more common among White women than Black or Latina women (p.001). Among women of color, tampon and menstrual cup use were greater among more highly educated women. Conversely, less educated women were more likely to use douches, feminine sprays, and scented tampons and pads (p.01). The highest prevalence of most fragranced product use was among Black women with HS education or less. CONCLUSIONS:White women with some college education have significantly different vaginal product use patterns than Black and Latina women without a college education. Racial/ethnic and socioeconomic patterns in product use may contribute to inequities in environmental exposures and health outcomes. In future analyses, we will examine intersectional patterns across multiple product categories. KEYWORDS: Environmental disparities, Female, Environmental epidemiology, Chemical exposures

Topical Probiotics for Women’s Urogenital Health: Selection of an Oil-based Carrier

Vaginal care products are widely used by women to relieve discomfort such as pain, itching and malodour, all of which are commonly caused by conditions resulting from microbiota dysbiosis. Previous studies showed that probiotic strains Lacticaseibacillus (formerly Lactobacillus) rhamnosus GR-1 (LGR-1) and Limosilactobacillus (formerly Lactobacillus) reuteri RC-14 (LRC-14), can aid in restoring homeostasis in the vaginal microbiome when taken orally. A topical product containing these strains could be of value for reducing malodour and improving quality of life. However, the formulation of such a product is a challenge, given that its ingredients must maintain shelf-life viability by excluding moisture. Here, we tested petroleum jelly, mineral oil, coconut oil, and olive oil for how well they maintained the viability of freeze-dried probiotic strains over a six-month timeframe. None of the oils caused excessive loss of bacterial viability, with petroleum jelly and coconut oil showing the most promise. Based on existing knowledge of these oils on the female genitalia, coconut oil and petroleum jelly could be suitable probiotic carriers for clinical testing.

Recent Advances in Polymer-Based Vaginal Drug Delivery Systems.

The vagina has been considered a potential drug administration route for centuries. Most of the currently marketed and investigated vaginal formulations are composed with the use of natural or synthetic polymers having different functions in the product. The vaginal route is usually investigated as an administration site for topically acting active ingredients; however, the anatomical and physiological features of the vagina make it suitable also for drug systemic absorption. In this review, the most important natural and synthetic polymers used in vaginal products are summarized and described, with special attention paid to the properties important in terms of vaginal application. Moreover, the current knowledge on the commonly applied and innovative dosage forms designed for vaginal administration was presented. The aim of this work was to highlight the most recent research directions and indicate challenges related to vaginal drug administrations. As revealed in the literature overview, intravaginal products still gain enormous scientific attention, and novel polymers and formulations are still explored. However, there are research areas that require more extensive studies in order to provide the safety of novel vaginal products.

Use and Acceptance of the Clinical Guide to Probiotic Products Available in Canada and in US: Translating Scientific Evidence to Clinical Practice Since 2008

ObjectivesThis clinical reference tool is independently designed to translate scientific evidence available up to date for commercially available probiotic products into practical, clinically relevant information, enabling clinicians to easily select the appropriate product, dose, and format for a specific indication. MethodsPublished studies with defined clinical outcomes for probiotic strain(s) were searched using defined inclusion criteria. Commercially available products containing said strain(s) were identified, and the Levels of Recommendation were used to rate the strength of the evidence. This information was compiled into a chart form, assessed by independent expert reviewers. This guide is a clinical decision-making tool to assist health care professionals in providing evidence-based recommendations for their patients. In the case of probiotics, the clinical evidence supports only certain formulations/brand names of the probiotics (including the genus, species, alphanumeric designation or strain, number of live bacteria present, the blend of probiotic strains present, and finally, the non-active ingredients present). The authors made every attempt to include the published clinical data for the available probiotic formulations. ResultsIn the clinical guide, the available strains were organized based on probiotic strain(s), doses, and evaluated evidence levels based on our pre-defined criteria. This document is easily accessible in print and digital formats (websites and mobile apps). ConclusionsThere is evidence to support the use of oral and vaginal probiotic products for various aspects of human health, however, applications and results are strain-specific and disease or symptom-specific. Due to frequent changes in commercial availability of probiotic strains, newly published evidence, and growing research, an annual review and updates of this Clinical Guide have been conducted since 2008. Lack of adverse effects supports the widespread use of these products, and further investigation is recommended. Funding SourcesAbstract submission is supported by an unrestricted education grant provided by the Alliance for Education on Probiotics.

Adaptation and validation of simple tools to screen and monitor for oral PrEP adherence.

Oral, vaginal and other pre-exposure prophylaxis (PrEP) products for HIV prevention are in various stages of development. Low adherence poses a serious challenge to successful evaluation in trials. In a previous study, we developed tools to screen for general adherence and specifically monitor intravaginal ring adherence within the context of HIV prevention clinical trials. This study aimed to further validate the screening tool and to adapt and provide initial psychometric validation for an oral pill monitoring tool. We administered a cross-sectional survey between June and October 2018 at a trial site located near Cape Town, South Africa, and another in Thika, Kenya, with 193 women who had experience using daily oral pills. We fit confirmatory factor analysis models on the screening tool items to assess our previously-hypothesized subscale structure. We conducted an exploratory factor analysis of oral PrEP monitoring items to determine the underlying subscale structure. We then assessed the construct validity of each tool by comparing subscales against each other within the current sample and against our original sample, from a study conducted in four sites in South Africa, including Cape Town. The screening tool structure showed moderate evidence of construct validity. As a whole, the tool performed in a similar way to the original sample. The monitoring tool items, which were revised to assess perceptions about and experiences using daily oral PrEP, factored into five subscales that showed moderate to good reliability. Four of the five subscales had a similar structure overall to the vaginal ring monitoring tool from which they were adapted. Accurate measurement of HIV-prevention product adherence is of critical importance to the assessment of product efficacy and safety in clinical trials, and the support of safe and effective product use in non-trial settings. In this study, we provide further validation for these measures, demonstrating the screening tool's utility in additional populations and adapting the monitoring tool's utility for different HIV-prevention products.

The Vaginal Microbiota, Bacterial Biofilms and Polymeric Drug-Releasing Vaginal Rings.

The diversity and dynamics of the microbial species populating the human vagina are increasingly understood to play a pivotal role in vaginal health. However, our knowledge about the potential interactions between the vaginal microbiota and vaginally administered drug delivery systems is still rather limited. Several drug-releasing vaginal ring products are currently marketed for hormonal contraception and estrogen replacement therapy, and many others are in preclinical and clinical development for these and other clinical indications. As with all implantable polymeric devices, drug-releasing vaginal rings are subject to surface bacterial adherence and biofilm formation, mostly associated with endogenous microorganisms present in the vagina. Despite more than 50 years since the vaginal ring concept was first described, there has been only limited study and reporting around bacterial adherence and biofilm formation on rings. With increasing interest in the vaginal microbiome and vaginal ring technology, this timely review article provides an overview of: (i) the vaginal microbiota, (ii) biofilm formation in the human vagina and its potential role in vaginal dysbiosis, (iii) mechanistic aspects of biofilm formation on polymeric surfaces, (iv) polymeric materials used in the manufacture of vaginal rings, (v) surface morphology characteristics of rings, (vi) biomass accumulation and biofilm formation on vaginal rings, and (vii) regulatory considerations.

Evaluation of systemic estrogen for preventing urinary tract infections in postmenopausal women.

Current guidelines for postmenopausal recurrent urinary tract infection (rUTI) prevention recommend the use of vaginal topical estrogen products but not systemic estrogens. Studies show that vaginal estrogen decreases the risk of rUTI, but evidence against use of systemic estrogen is less convincing. We performed a comprehensive literature review to evaluate the effect of systemic estrogen on UTI occurrence among postmenopausal women. MEDLINE (PubMed), EMBASE, and CINAHL were searched for manuscripts published in English between January 1990 and July 2020. The search terms were "urinary tract infection" and "estrogen." Inclusion criteria were studies of postmenopausal women who received systemic estrogen therapy (any regimen) that reported UTI frequency during any follow-up period. Case studies, commentaries, and reviews were excluded. A priori specifications of seven study criteria were set representing the ideal study for assessing efficacy of systemic estrogen for rUTI prevention and were used to evaluate each included study. Searches identified 281 results, and after deduplication and review, 8 studies met inclusion criteria: 4 randomized controlled trials, 1 secondary analysis of a randomized controlled trial, 1 prospective cohort study, 1 case-control study, and 1 cross-sectional study. Of the eight included studies, only two enrolled postmenopausal women with a rUTI diagnosis, four had sufficient sample size to detect a clinically meaningful difference between systemic estrogen versus placebo, two used dosage regimens anticipated to achieve a therapeutic effect, and three assessed UTI rates for an adequate duration of 6 months or more (the standard minimum duration of time needed to make a diagnosis of rUTI). Overall, none of the studies met all predefined criteria for the ideal study to assess the efficacy of systemic estrogen for rUTI prevention. UTIs will continue to be a significant cause of morbidity and hospitalizations in postmenopausal women unless more research is done to better understand the role of estrogen on UTI rates. The evidence arguing use (or abandonment) of systemic estrogen for the prevention of rUTI is based on few studies with substantial methodologic limitations; there is significant room for improvement.

Potential of mucoadhesive chitosan glutamate microparticles as microbicide carriers – antiherpes activity and penetration behavior across the human vaginal epithelium

Chitosan glutamate (gCS) spray-dried microparticles appear promising carriers to overcome challenges associated with vaginal microbicide delivery. This study aimed at elucidating the penetration and mucoadhesive behavior of developed gCS multiunit carriers with zidovudine (ZVD) as a model antiretroviral agent in contact with excised human vaginal epithelium followed with an examination of in vitro antiherpes activity in immortal human keratinocytes HaCaT and human vaginal epithelial cells VK2-E6/E7. Both ZVD dispersion and placebo microparticles served as controls. Microparticles displayed feasible (comparable to commercial vaginal product) mucoadhesive and mucoretention characteristics to isolated human vaginal tissue. Ex vivo penetration studies revealed that gCS increased the accumulation of active agent in the vaginal epithelium but surprisingly did not facilitate its penetration across human tissue. Finally, the obtained antiviral results demonstrated the potential of gCS as an antiherpes adjunctive, whose mode of action was related to blocking viral attachment.