Aloe Vera; A new treatment for atrophic vaginitis, A randomized double-blinded controlled trial.

AIM OF THE STUDY: Vaginal atrophy is of the most common problems during menopause with significant psychosocial and medical consequences. Estrogen as an approved therapy for vaginal atrophy can be associated with adverse effects and several contraindications in menopause patients. The aim is to compare the effect of Aloe Vera vaginal cream with commercially available estrogen vaginal cream for management of vaginal atrophy in menopause females. MATERIALS AND METHODS: This is a double-blinded randomized controlled trial on 60menopause female with complaints of vaginal atrophy symptoms. Subjects were randomly allocated in two groups of 30 patients, named as estrogen and Aloe Vera groups. Vaginal health index (VHI), maturity value (MV), vaginal cytologic smear, transvaginal sonography (TVS) and severity of symptoms related to vaginal atrophy were assessed before and after 6-weeks of vaginal cream administration. RESULTS: Comparison of MV before and after treatment revealed that superficial cells were significantly increased after administration of both vaginal cream (6.67 VS 54.33 in Aloe Vera group; 4.33 VS 59.67 in estrogen group). In addition, VHI (13.83 vs 20.13 in Aloe Vera group; 13.97 vs 19.93 in estrogen group) and symptoms of vaginal atrophy (3.63 vs 1.10 in Aloe Vera group; 3.90 vs 0.66 in estrogen groups) were also significantly improved after treatment in both groups. There was no significant difference between groups after treatment except for fluid volume with a superiority in Aloe Vera group (P-value = 0.004) CONCLUSION: Aloe Vera vaginal cream can be as effective as estrogen vaginal cream in the management of vaginal atrophy in menopause females.

Efficacy of a vaginal tablet as a Persian medicine product on vulvovaginal candidiasis: a double-blind, randomised, placebo-controlled trial.

Context: In Persian medicine, topical ingredients such as Rosa damascena Mill. (Rosaceae), are usually recommended for the treatment of uterine diseases. Scientific evaluation of these historical documents can be valuable for finding new potential use in conventional medicine.Objective: This clinical trial was performed to determine whether the use of the 'ward' vaginal tablet, which contains Rosa damascena, Punica granatum L. (Punicaceae), Querqus infectoria Oliv. (Fagaceae), Myrtus communis L. (Myrtaceae) and Nardostachys jatamansi (D.Don) DC. (Caprifoliaceae) could alleviate the symptoms of vulvovaginal candidiasis.Materials and methods: A parallel double-blinded placebo-controlled study was done. Eighteen to fifty-year-old women with vulvovaginal candidiasis were divided into the 'ward' and placebo groups, 46 individuals in each group. The 'ward' group received the 'ward' vaginal tablet containing 200 mg of dried extract. Placebo group received a placebo (composed of corn starch and lactose). One tablet was applied through the vagina for 7 consecutive nights.Results: Two weeks after medication administration, the vaginal discharge sample of patients was re-cultured; 29 patients (63.045%) in the 'ward' group and 6 (13.04%) patients in the placebo group had negative culture (p < 0.001). All clinical symptoms including itching, irritation, and vaginal discharge were significantly reduced in the 'ward' group compared with the placebo group following the intervention and the follow up (p < 0.05).Discussion and conclusions: The findings suggest the 'ward' vaginal tablet could ameliorate vulvovaginal candidiasis. Future larger studies are recommended due to compare the therapeutic effect of the 'ward' vaginal tablet with common treatments.

Development and in vivo evaluation of chitosan-gel containing Mitracarpus frigidus methanolic extract for vulvovaginal candidiasis treatment.

Vulvovaginal candidiasis (VVC) is characterized by inflammatory changes in the vaginal mucosa caused by abnormal colonization of Candida species. Traditional topical therapies using reference antifungal drugs usually present several issues and limitations for VVC treatment. Thus, the interest in new vaginal formulations, mainly those based on compounds from natural origin, has been growing over the last years. Methanolic extract from the plant species Mitracarpus frigidus (Willd. Ex Reem Schult.) K. Schum (MFM) has presented potential antifungal activity against C. albicans vaginal infection. Here, we aimed to develop and characterize a gynecological gel formulation based on chitosan containing MFM and to evaluate its anti-C. albicans effectiveness in the treatment of VVC. First, MFM was incorporated into a gel formulation based on chitosan in three final concentrations: 2.5 %, 5.0 %, and 10.0 %. Next, these gel formulations were subjected to stationary and oscillatory rheological tests. Finally, the gel was tested in an experimental VVC model. The rheological tests indicated pseudoplastic fluids, becoming more viscous and elastic with the increase of the extract concentration, indicating intermolecular interactions. Our in vivo analyses demonstrated a great reduction of vulvovaginal fungal burden and infection accompanied with the reduction of mucosal inflammation after MFM chitosan-gel treatment. The present findings open perspectives for the further use of the MFM-chitosan-gel formulation as a therapeutic alternative for VVC treatment.

Comparison of Pueraria mirifica gel and conjugated equine estrogen cream effects on vaginal health in postmenopausal women.

OBJECTIVES: To compare the effects of a 12-week treatment with Pueraria mirifica (PM) gel or a conjugated estrogen cream on vaginal maturation index, vaginal symptom score, vaginal health assessment score, and vaginal flora in postmenopausal women. METHODS: In a prospective, noninferiority, randomized controlled study, 82 postmenopausal women with at least one vulvovaginal symptom, that is, dryness, soreness, irritation, dyspareunia, or discharge, were recruited. Participants were randomly assigned into two groups for treatment with either PM gel or conjugated estrogen cream (CEE). The treatment regimen consisted of application of 0.5 g of product intravaginally daily for 2 weeks, and then decreased to three times per week for 10 weeks. Vaginal maturation index, vaginal symptoms score, and vaginal health assessment score were evaluated before the beginning of the study and at 6 weeks and 12 weeks after treatment with PM or CEE. RESULTS: The vaginal maturation index increased significantly in both treatment groups at week 12, from 22.44 ±â€Š22.28 to 47.56 ±â€Š29.00 and from 27.07 ±â€Š26.12 to 66.90 ±â€Š22.42 in the PM and the CEE groups, respectively (P < 0.05). A significantly higher effect was, however, observed in the CEE group (P < 0.05). Vaginal symptom scores decreased significantly after treatment in both groups, from 4.37 ±â€Š2.79 to 0.95 ±â€Š1.88 and from 4.15 ±â€Š2.16 to 0.68 ±â€Š1.64 in the PM and the CEE groups, respectively (P < 0.05), with no statistically significant different between the two groups (P > 0.05). CONCLUSIONS: The use of a 12-week treatment regimen with Pueraria mirifica gel was shown to be efficacious and safe for the treatment of vulvovaginal atrophy. Conjugated estrogen cream was found to be more effective compared to Pueraria mirifica gel in improving signs of vaginal atrophy and restoring vaginal epithelium at 6 and 12 weeks.

Comparing the effects of Calendula officinalis and clotrimazole on vaginal Candidiasis: A randomized controlled trial.

This triple-blind trial examined the effects of Calendula officinalis vaginal cream on the treatment of vaginal Candidiasis (primary outcome) and sexual function (secondary outcome). Married women aged 18-45 years with vaginal Candidiasis (n = 150) were recruited from April to October 2014 and randomized into Calendula and clotrimazole groups, using 5-g vaginal cream every night for seven nights. Clinical and laboratory assessments were conducted at 10-15 and 30-35 days after intervention and the female sexual function index was assessed at 30-35 days. Six women were lost to follow-up. The frequency of testing negative for Candidiasis in the Calendula group was significantly lower at the first (49% vs. 74%; odds ratio (OR) 0.32; 95% confidence interval (CI) 0.16-0.67) but higher at the second (77% vs. 34%; OR 3.1; 95% CI 1.5-6.2) follow-up compared to the clotrimazole group. The frequency of most signs and symptoms were almost equal in the two groups at the first follow-up, but were significantly lower in the Calendula group at the second follow-up. Sexual function had almost equal significant improvement in both groups. Calendula vaginal cream appears to have been effective in the treatment of vaginal Candidiasis and to have a delayed but greater long-term effect compared to clotrimazole.

New strategies for local treatment of vaginal infections.

Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route.

Mucoadhesive and thermogelling systems for vaginal drug delivery.

This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described.

Blockade of tubal patency following transcervical administration of polidocanol foam: initial studies in rhesus macaques.

OBJECTIVE: To demonstrate the feasibility of polidocanol foam (PF) as a nonsurgical method of female permanent contraception using a nonhuman primate model. STUDY DESIGN: Four groups of adult female rhesus macaques underwent either transcervical treatment with 5% PF directly into the uterine cavity, treatment with inert (methylcellulose, MF) foam or no treatment followed by removal of the reproductive tract for histologic evaluation. Untreated animals were included in Group 1 (n=3). Group 2 animals (n=4) were treated once with MF. Group 3 (n=7) received a single, and Group 4 (n=5) received multiple monthly treatments with PF; in these 2 groups, baseline tubal patency was assessed either laparoscopically by chromopertubation (CP) or by hysterosalpingography. RESULTS: Group 1 (untreated) and Group 2 (MF) animals had normal tubal histology. In contrast, Group 3 and 4 females treated with PF showed evidence of tubal damage. In Group 4, bilateral tubal blockade was noted on CP after two (n=2) or three (n=3) treatments. Histologic analysis confirmed complete tubal occlusion (loss of epithelium, fibrosis) in three of these animals, and one showed significant tubal damage localized to the intramural segment. Nontarget (cervix, vagina, endometrium, ovary) reproductive tissues were unaffected. While similar tubal changes were observed after a single treatment (Group 3), endometrial hemorrhage was also noted as an acute change. CONCLUSION: PF is a promising candidate agent for nonsurgical permanent female contraception. The histologic features of PF occlusion are confined to the intramural portion of the tube. IMPLICATIONS: This study in rhesus macaques supports further development of transcervical administration of PF as a nonsurgical approach to permanent contraception. A nonsurgical method could reduce risks and costs associated with surgical female sterilization and increase access to permanent contraception.

A combination microbicide gel protects macaques against vaginal simian human immunodeficiency virus-reverse transcriptase infection, but only partially reduces herpes simplex virus-2 infection after a single high-dose cochallenge.

Herpes simplex virus-2 (HSV-2) infection increases HIV susceptibility. We previously established a rhesus macaque model of vaginal HSV-2 preexposure followed by cochallenge with HSV-2 and simian/human immunodeficiency virus-reverse transcriptase (SHIV-RT). Using this model, we showed that a gel containing the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan (CG) reduced SHIV-RT infection. To evaluate the efficacy of new generation microbicides against both viruses, we first established dual infection after single vaginal cochallenge with SHIV-RT and HSV-2 in HSV-2-naive macaques. All animals (6/6) became HSV-2 infected, with 4/6 coinfected with SHIV-RT. In a control group cochallenged with SHIV-RT and UV-inactivated HSV-2, 2/4 became SHIV-RT infected, and none had detectable HSV-2. Low-level HSV-2-specific antibody and T cell responses were detected in some HSV-2-infected animals. To test a CG gel containing MIV-150 and zinc acetate (MZC), which provided naive animals full protection from SHIV-RT for at least 8 h, MZC (vs. CG) was applied daily for 14 days followed by cochallenge 8 h later. MZC prevented SHIV-RT infection (0/9 infected, p=0.04 vs. 3/6 in CG controls), but only reduced HSV-2 infection by 20% (6/9 infected vs. 5/6 in CG, p=0.6). In HSV-2-infected animals, none of the gel-treated animals seroconverted, and only the CG controls had measurable HSV-2-specific T cell responses. This study shows the promise of MZC to prevent immunodeficiency virus infection (even in the presence of HSV-2) and reduce HSV-2 infection after exposure to a high-dose inoculum. Additionally, it demonstrates the potential of a macaque coinfection model to evaluate broad-spectrum microbicides.

Improvement of an encapsulation process for the preparation of pro- and prebiotics-loaded bioadhesive microparticles by using experimental design.

The purpose of this study was to design a new vaginal bioadhesive delivery system based on pectinate-hyaluronic acid microparticles for probiotics and prebiotics encapsulation. Probiotic strains and prebiotic were selected for their abilities to restore vaginal ecosystem. Microparticles were produced by emulsification/gelation method using calcium as cross-linking agent. In the first step, preliminary experiments were conducted to study the influence of the main formulation and process parameters on the size distribution of unloaded microparticles. Rheological measurements were also performed to investigate the bioadhesive properties of the gels used to obtain the final microparticles. Afterwards an experimental design was performed to determine the operating conditions suitable to obtain bioadhesive microparticles containing probiotics and prebiotics. Experimental design allowed us to define two important parameters during the microencapsulation process: the stirring rate during the emulsification step and the pectin concentration. The final microparticles had a mean diameter of 137µm and allowed a complete release of probiotic strains after 16h in a simulated vaginal fluid at +37°C.

Acceptability and adherence: findings from a Phase II study of a candidate vaginal microbicide, 'Praneem polyherbal tablet', in Pune, India.

Acceptability and adherence in clinical trials of microbicides may possibly predict their acceptance by the community. In this study, we investigated the acceptability and adherence of Praneem polyherbal tablet, a candidate microbicide, among 100 HIV-uninfected participants of a Phase II randomised, double-blind, placebo-controlled trial in Pune, India, conducted between June 2004 and February 2006 involving 6 months of coitally-dependent product use. The relationship between five acceptability domains and adherence to product use during the study period was explored. Acceptability and adherence were assessed among 95 study participants completing all study follow-ups. One hundred percent adherence (product use during each sex act for the study period) was reported by 67 participants (70.5%). The majority of participants reported acceptability towards all product characteristics. Product odour was reported to be a concern both in the placebo and Praneem arms. Participants from the Praneem arm [adjusted odds ratio (AOR)=3.8; 95% CI 1.4-10.8] and participants reporting lower acceptability for experience of product use during the sex act (AOR=4.2; 95% CI 1.0-17.3) were more likely to have partial adherence. In conclusion, the study product was acceptable to the majority of participants. However, barriers to adherence attributable to undesirable sexual experiences need to be addressed.

Chitosan citrate as multifunctional polymer for vaginal delivery. Evaluation of penetration enhancement and peptidase inhibition properties.

In the present work the employment of chitosan citrate (Chs citrate) as multifunctional polymer in vaginal applications was evaluated. Potential properties of penetration enhancement and protease inhibition could be expected because of the capability of citrate to bind divalent cations such as calcium, that is involved in the regulation of gap and tight junctions, and zinc, that is essential co-factor for some proteases. A comparison was performed with chitosan HCl (Chs HCl). Ex vivo drug permeation experiments were performed on pig vaginal mucosa, by application of 3.0% (w/w) chitosan gels. Acyclovir (5.0%, w/w) and ciprofloxacin HCl (0.3%, w/w) were used as low molecular weight model drugs. Fluorescein isothiocyanate dextran MW 4400 (FD4) was used as hydrophilic high molecular weight fluorescent probe (0.2%, w/w). In the case of low MW drugs the amount penetrated into pig vaginal mucosa was measured by extraction from tissue slices and HPLC detection. From the samples maintained in contact with FD4, slices were cut perpendicularly to the surface and observed by means of confocal laser scanning microscopy (CLSM). FD4 permeation was also measured in in-vitro cell culture model (Caco-2). The penetration enhancing capacity of Chs citrate was comparable to that of Chs HCl. Both Chs citrate and Chs HCl were tested for the inhibition of the proteolytic enzymes carboxypeptidase A and leucine aminopeptidase. In both cases Chs citrate showed a significantly higher inhibition of enzymatic activity with respect to Chs HCl.

Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole:beta-cyclodextrin complex.

The purpose of this study was to achieve a better therapeutic efficacy and patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with mucoadhesive polymers such as Carbopol 934 and hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility, clotrimazole was incorporated as its inclusion complex with 1:1 molar ratio with beta-cyclodextrin. The inclusion complex was thoroughly characterized using various techniques, including 1H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility studies, and determination of stability constant (k(1:1)). The gelation temperature and rheological behavior of different formulations at varying temperatures were measured. In vitro release profiles of the gels were determined in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin slowed down the release of clotrimazole considerably. Carbopol 934, on the other hand, was found to interact with beta-cyclodextrin, inducing precipitation. As far as rheological properties are concerned, thermosensitive in situ gelling was obtained with formulations containing drug:cyclodextrin complex rather than with free drug. Thus, the optimum formulation for a controlled-release thermosensitive and mucoadhesive vaginal gel was determined to be clotrimazole:beta-cyclodextrin 1% with 0.2% hydroxypropylmethylcellulose in Pluronic F127 gel (20%) providing continuous and prolonged release of active material above MIC values.

Can local application of imiquimod cream be an alternative mode of therapy for patients with high-grade intraepithelial lesions of the vagina?

The aim of the present study was to assess the local application of imiquimod cream 5% as an alternative mode of therapy for high-grade vaginal intraepithelial neoplasia (VAIN 2/3). Positive human papillomavirus (HPV) patients with multifocal high-grade VAIN (2/3) not involving the vaginal vault in hysterectomized patients took part in this study. The treatment consisted of vaginal application of the cream under colposcopic guidance. Following management, biopsies were obtained from the previously recorded lesions. p53 expression was recorded prior and after therapy. Seven patients with VAIN 2/3 took part in this study. Six patients (86%) were positive for high-risk HPV type while three (43%) women who were positive for p53 nuclei prior to therapy were found to be negative following treatment. After treatment, 86% of the patients were found to have either HPV infection or low-grade VAIN. During follow-up, two patients (28.5%) were managed by vaginectomy, one for persistent and one for recurrent high-grade VAIN. Currently, from the five patients that are followed, three have simple HPV infection and two, VAIN 1. Imiquimod cream 5% might represent an alternative although not permanent method of management in young, HPV-positive women with multifocal high-grade lesions of the vagina (VAIN 2/3).

Mucosal toxicity studies of a gel formulation of native pokeweed antiviral protein.

Pokeweed antiviral protein (PAP), a 29-kDa plant-derived protein isolated from Phytolacca americana, is a promising nonspermicidal broad-spectrum antiviral microbicide. This study evaluated the mucosal toxicity potential of native PAP in the in vivo rabbit vaginal irritation model as well as the in vitro reconstituted human vaginal epithelial tissue model. Twenty-two New Zealand white rabbits in 4 subgroups were exposed intravaginally to a gel with and without 0.01, 0.1, or 1.0% native PAP for 10 consecutive days. The dose of PAP used represented nearly 200- to 20,000 times its in vitro anti-HIV IC50 value. Animals were euthanized on day 11 and vaginal tissues were evaluated for histologic and immunohistochemical evidence of mucosal toxicity, cellular inflammation, and hyperplasia. Blood was analyzed for changes in hematology and clinical chemistry profiles. Reconstituted human vaginal epithelial tissue grown on membrane filters was exposed to 0.01, 0.1, or 1.0% native PAP in medium or topically via a gel for 24 hours and tissue damage was evaluated by histological assessment. In the in vivo rabbit vaginal irritation model, half of all PAP-treated rabbits (8/16) exhibited an acceptable range of vaginal mucosal irritation (total score <8 out of a possible 16), whereas nearly a third of PAP-treated rabbits (5/16) developed moderate to marked vaginal mucosal irritation (total score >11). However, no treatment-related adverse effects were seen in hematological or clinical chemistry measurements. Furthermore, in vitro exposure of a 3-dimensional human vaginal tissue grown on polycarbonate membrane filters to identical concentrations of PAP either added to culture medium or applied topically via gel formulation did not result in direct toxicity as determined by histologic evaluation. These findings indicate careful monitoring of vaginal irritation will be required in the clinical development of PAP as a nonspermicidal microbicide.

The evaluation of the local tolerance of vaginal formulations, with or without nonoxynol-9, using the slug mucosal irritation test.

BACKGROUND: Frequent use of some vaginal formulations can induce mucosal irritation. Therefore, it is important to evaluate their vaginal tolerance. GOAL: The goal of this study was to optimize the mucosal irritation test using slugs for the evaluation of the local tolerance of vaginal gels and investigate the relevance of the test. STUDY DESIGN: The irritation potential of the gels was assessed by the amount of mucus produced during a repeated 30-minute contact period. Membrane damage was estimated from the release of proteins and enzymes. After optimization of the procedure, the local tolerance of several vaginal gels was evaluated. RESULTS: Hydroxyethyl cellulose gel induced no irritation, because the mucus production and the protein release were low and no enzyme release was detected. Replens and K-Y jelly resulted in an increased mucus production; however, no increased protein and no enzyme release were detected. The nonoxynol-9-containing gels Protectaid, Advantage S, and Conceptrol caused a higher mucus production and an increased protein release and/or enzyme release, indicating severe irritation. CONCLUSION: The mucosal irritation test using slugs can be used for local tolerance testing of vaginal formulations.

A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole.

The development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-beta-cyclodextrin (HPbetaCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPbetaCD. After pH adjustment, the itraconazole/HPbetaCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPbetaCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis.

Entry of inflammatory cells into the mouse vagina following application of candidate microbicides: comparison of detergent-based and sulfated polymer-based agents.

BACKGROUND: Because topical microbicides designed to prevent the spread of sexually transmitted diseases may be applied frequently, it is important to ensure product safety as well as efficacy. A murine model was developed to test for induction of inflammatory responses following application of candidate microbicides. GOAL: A comparison was made of the induction of inflammation following vaginal application of detergent-based and sulfated polymer-based microbicides. STUDY DESIGN: Vaginal leukocytes were collected, identified, and quantified following microbicide application to detect the entry of inflammatory leukocytes into the vaginal lumen. RESULTS: Large numbers of neutrophils and macrophages entered the vaginal lumen following a single application of detergent-based microbicides. No significant increase in vaginal leukocytes was detected following a single or repeated application of sulfated polymer-based microbicides. CONCLUSION: Application of sulfated polymer-based microbicides was less likely to result in inflammatory responses than was application of detergent-based compounds. This murine model should prove useful as part of a screening process to prioritize candidate microbicides before clinical trial.

GM-144, a novel lipophilic vaginal contraceptive gel-microemulsion.

In a systematic effort to develop a dual-function intravaginal spermicide as well as a drug delivery vehicle against sexually transmitted pathogens, a submicron particle size (30-80 nm), lipophilic and spermicidal gel-microemulsion (viz GM-144) containing the pharmaceutical excipients propylene glycol, Captex 300, Cremophor EL, Phospholipon 90G, Rhodigel, Pluronic F-68, and sodium benzoate was formulated. GM-144 completely immobilized sperm in human or rabbit semen in less than 30 seconds. Therefore, the in vivo contraceptive potency of intravaginally applied GM-144 was compared in the standard rabbit model to those of the detergent spermicide, nonoxynol-9 (N-9)-containing formulation. Eighty-four ovulated New Zealand White rabbits in subgroups of 28 were artificially inseminated with and without intravaginal administration of GM-144 or 2% N-9 (Gynol II) formulation and allowed to complete term pregnancy. GM-144 showed remarkable contraceptive activity in the rigorous rabbit model. When compared with control, intravaginal administration of GM-144 and Gynol II resulted in 75% and 70.8% inhibition of fertility (P <.0001 versus control, Fisher's exact test), respectively. Thus, GM-144 as a vaginal contraceptive was as effective as the commercially available N-9 gel. In the rabbit vaginal irritation test, none of the 6 rabbits given daily intravaginal application of spermicidal GM-144 for 10 days developed epithelial ulceration, edema, leukocyte influx, or vascular congestion characteristic of inflammation (total score = 5). Therefore, GM-144 has the potential to become a clinically useful safe vaginal contraceptive and a vehicle for formulating lipophilic drugs used in reducing the risk of heterosexual transmission of sexually transmitted diseases.