Data on statistical experimental design to formulate amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid for the treatment of vulvovaginal candidiasis.
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ABSTRACT: Data described in this article are related to the research article entitled "Amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid (AMP EUD nanoparticles/HA) for the treatment of vulvovaginal candidiasis" [1]. In this work, we report original data on the statistical experimental design to formulate uncoated AMP EUD nanoparticles, data on the validation of spectrophotometric method to quantify the AMP released from uncoated EUD nanoparticles and coated with HA to obtain the in vitro drug release profiles as well as the drug encapsulation efficiency. In addition, we describe original data on characterization, including diameter size, polydispersity index, zeta potential, FTIR, DSC/TG, and XRD; data on diameter of in vitro inhibition halos of Candida albicans; and on the vaginal burden of infected animals treated with uncoated AMP EUD nanoparticles and AMP EUD nanoparticles/HA. Finally, different histological sections of endocervix collected from treated and untreated animals were inserted into this manuscript.
Project description:Evaluation of bacteriome and mycobiome in patients with acute vulvovaginal candidiasis before, during and after treatment with a gel containing a Lactobacillus mixture
Project description:Recurrent vulvovaginal candidiasis (RVVC) and vulvovaginal candidiasis (RVVC) are one of the most common gynecological infections, primarily caused by Candida species. Although risk factors of RVVC and VVC have been identified in many studies, antifungal immunological mechanisms are still not fully understood. We performed a 1-year prospective study in a local hospital to monitor 98 patients clinically diagnosed with gynecological Candida infection. The results showed that 20.41% (20/98) are with RVVC, and 79.59% (78/98) patients have VVC. C. albicans accounts for 90% and 96.1% of all strains isolated collected from RVVC and VVC patients, respectively. Antifungal susceptibility testing showed no significant difference in Candida species between RVVC and VVC patients. However, the serum levels of IFN-γ, TNF-α, and IL-17F in the RVVC group were significantly lower than those of the VVC group, while IL-4, IL-6, and IL-10 were higher in the RVVC patients than VVC patients. IL-17A and IL-2 levels were comparable between the two groups. Taken together, our results suggest that the host-immune responses, especially Th1/2 immunity, may play important roles in prognosis of RVVC and VVC.
Project description:Chitosan nanoparticles have gained attention as drug delivery systems (DDS) in the medical field as they are both biodegradable and biocompatible with reported antimicrobial and anti-leishmanial activities. We investigated the application of chitosan nanoparticles as a DDS for the treatment of cutaneous leishmaniasis (CL) by preparing two types of chitosan nanoparticles: positively charged with tripolyphosphate sodium (TPP) and negatively charged with dextran sulphate. Amphotericin B (AmB) was incorporated into these nanoparticles. Both types of AmB-loaded nanoparticles demonstrated in vitro activity against Leishmania major intracellular amastigotes, with similar activity to unencapsulated AmB, but with a significant lower toxicity to KB-cells and red blood cells. In murine models of CL caused by L. major, intravenous administration of AmB-loaded chitosan-TPP nanoparticles (Size = 69 ± 8 nm, Zeta potential = 25.5 ± 1 mV, 5 mg/kg/for 10 days on alternate days) showed a significantly higher efficacy than AmBisome® (10 mg/kg/for 10 days on alternate days) in terms of reduction of lesion size and parasite load (measured by both bioluminescence and qPCR). Poor drug permeation into and through mouse skin, using Franz diffusion cells, showed that AmB-loaded chitosan nanoparticles are not appropriate candidates for topical treatment of CL.
Project description:Candida albicans, along with other closely related Candida species, are the primary causative agents of vulvovaginal candidiasis (VVC)-a multifactorial infectious disease of the lower female reproductive tract resulting in pathologic inflammation. Unlike other forms of candidiasis, VVC is a disease of immunocompetent and otherwise healthy women, most predominant during their child-bearing years. While VVC is non-lethal, its high global incidence and profound negative impact on quality-of-life necessitates further understanding of the host and fungal factors that drive disease pathogenesis. In this review, we cover the current state of our understanding of the epidemiology, host response, fungal pathogenicity mechanisms, impact of the microbiome, and novel approaches to treatment of this most prevalent human candidal infection. We also offer insight into the latest advancements in the VVC field and identify important questions that still remain.
Project description:PurposeThis study aimed at establishing the link between clinical manifestations, microbiological diagnosis and the therapeutically approach in the treatment of vulvovaginitis candidosa in childhood.Patients and methods35 patients aged 1-18 years were studied and divided into two groups. The criteria for establishing the diagnosis included the clinical symptoms, the native microscopic investigations and the microbiological control of the materials taken on the 14th and 30th day before and after treatment by means of a vaginal swab.ResultsEtiologically, vulvovaginitis was diagnosed as candidose in 35.71% and 80.95% for the two groups, respectively, by means of the native microscopic preparation. The mycological investigations confirmed the diagnosis in 23.81% of the cases. Other bacterial findings included enterococci, intestinal bacteria and staphylococci. Positive results of the local and combined therapy were reported in 67% of the cases on the 14th day, and in 65%--on the 30th day.ConclusionsVaginal fluorine tends to persist as compared to the remaining symptoms. Vulvovaginitis candidosa most commonly occurs in conjunction with other specific bacteria. Local therapy is recommended in acute infections and the combined therapy is more efficient in chronic conditions. Combined treatment should be administered in at least two 10-day courses because of a tendency to recurrence.
Project description:Recruitment of polymorphonuclear neutrophils (PMNs) into the vaginal lumen is the hallmark of an acute immunopathologic inflammatory response during vulvovaginal candidiasis (VVC) caused by Candida albicans. Recurrent VVC (RVVC) remains a chronic health burden in affected women worldwide despite the use of antifungal therapy. Based on the role leukotrienes (LTs) play in promoting inflammation, leukotriene receptor antagonists (LTRAs) targeted for LTB4 (etalocib) or LTC4, LTD4, and LTE4 (zafirlukast or montelukast) have been shown to reduce inflammation of epithelial tissues. An open-label pilot study using long-term regimens of zafirlukast in women with RVVC indicated the potential for some relief from recurrent episodes. To investigate this clinical observation further, we evaluated the effects of LT antagonistic agents and LT deficiency on the immunopathogenic response in a mouse model of VVC. Results showed that mice given daily intraperitoneal injections of individual LTRAs, starting 2days prior to vaginal inoculation with C. albicans and continuing through 14days post-inoculation, had no measurable reduction in PMN migration. The LTRAs were also ineffective in reducing levels of the hallmark vaginal inflammatory markers (S100A8, IL-1β) and tissue damage (LDH) associated with the immunopathogenic response. Finally, LT-deficient 5-lipoxygenase knockout mice showed comparable levels of vaginal fungal burden and PMN infiltration to wild-type mice following inoculation with a vaginal (ATCC 96113) or laboratory (SC5314) C. albicans isolate. These results indicate that despite some clinical evidence suggestive of off-target efficacy of LTRAs in RVVC, LTs and associated signaling pathways appear to be dispensable in the immunopathogenesis of VVC.
Project description:PurposeVulvovaginal candidiasis (VVC) is a mucosal infection of the female lower genital tract for which treatment using conventional antifungal drugs shows limited effectiveness. Herein, amphotericin B-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (AmB-NPs) were fabricated and combined with low intensity ultrasound (US) to mediate AmB-NPs intravaginal drug delivery to achieve productive synergistic antifungal activity in a rabbit model of VVC.MethodsPolymeric AmB-NPs were fabricated by a double emulsion method and the physical characteristics and biosafety of nanoparticles were analyzed. The distribution and tissue permeability of nanoparticles after intravaginal ultrasound irradiation (1.0 MHz, 1.0 W/cm2, 5 min, 50% duty ratio) were observed in the vagina. The synergistic therapeutic activity of US-mediated AmB-NPs treatment was evaluated using an experimental rabbit model of VVC. Vaginal C. albicans colony counts, the pathological structure of the vagina epithelium, and Th1/Th2/Th17-type cytokine and oxidative stress levels were analyzed to investigate the therapeutic effect in vivo.ResultsThe prepared AmB-NPs showed an obvious shell and core structure with uniform size and good dispersion and displayed high biosafety and US-sensitive slow drug release. Ultrasound significantly enhanced nanoparticle transport through the mucus and promoted permeability in the vaginal tissue. US-mediated AmB-NPs treatment effectively increased drug sensitivity, even in the presence of the vaginal mucus barrier in vitro. On the seventh day after treatment in vivo, the combination treatment of AmB-NPs and US significantly reduced the fungal load in the vagina, achieving over 95% clearance rates, and also improved the pathological epithelium structural damage and glycogen secretion function. The expression of Th1 (IFN-γ, IL-2) and Th17 (IL-17) cytokines were significantly increased and Th2 (IL-6, IL-10) cytokines significantly decreased in the US + AmB-NP group. Furthermore, US-mediated AmB-NPs treatment effectively increased C. albicans intracellular reactive oxygen species (ROS) levels and promoted vaginal oxidation and antioxidants to normal levels.ConclusionUS-mediated drug-loaded nanoparticles with intravaginal drug delivery exhibited a productive synergistic antifungal effect, which may provide a new non-invasive, safe, and effective therapy for acute or recurrent fungal vaginitis.
Project description:Background: Recurrent vulvovaginal candidiasis (RVVC), defined as three or more confirmed infections over 1 year, occurs in up to 10% of women. In these women, the objective is often symptomatic control rather than mycologic cure. Current Centers for Disease Control and Prevention (CDC) guidelines recommend oral fluconazole as first-line maintenance, but state if this oral regimen is not feasible, intermittent topical treatments can be considered. No specific recommendations for type or frequency of topical applications are provided by the CDC. Methods: A panel of vulvovaginal experts convened to develop a consensus recommendation for topical maintenance dosing for RVVC. Results: Data suggest that clotrimazole, miconazole, terconazole, and intravaginal boric acid are suggested recommendations for recurrent vulvovaginitis caused by both Candida albicans and nonalbicans species. Nystatin ovules may not be as effective as azoles. Identification of species will influence treatment decisions. In addition, treatment may be modified based on prior response to a specific agent, especially in nonalbicans species. Fluconazole, ibrexafungerp, and intravaginal boric acid should be avoided during pregnancy. Conclusions: The expert consensus for women with RVVC is an initial full course of treatment followed by topical maintenance beginning at one to three times weekly, based on chosen agent. Twice a week dosing was the regimen most often utilized. In some women, episodic treatment may be used, but maintenance should remain an option for this population.
Project description:Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases, and there are controversial reports regarding the diversity of the associated vaginal microbiota. We determined the vaginal microbial community in patients with VVC, bacterial vaginosis (BV), and mixed infection of VVC and BV using Illumina sequencing of 16S rRNA tags. Our results revealed for the first time the highly variable patterns of the vaginal microbiome from VVC patients. In general, the alpha-diversity results of species richness and evenness showed the following order: normal control < VVC only < mixed BV and VVC infection < BV only. The beta-diversity comparison of community structures also showed an intermediate composition of VVC between the control and BV samples. A detailed comparison showed that, although the control and BV communities had typical patterns, the vaginal microbiota of VVC is complex. The mixed BV and VVC infection group showed a unique pattern, with a relatively higher abundance of Lactobacillus than the BV group and higher abundance of Prevotella, Gardnerella, and Atopobium than the normal control. In contrast, the VVC-only group could not be described by any single profile, ranging from a community structure similar to the normal control (predominated with Lactobacillus) to BV-like community structures (abundant with Gardnerella and Atopobium). Treatment of VVC resulted in inconsistent changes of the vaginal microbiota, with four BV/VVC samples recovering to a higher Lactobacillus level, whereas many VVC-only patients did not. These results will be useful for future studies on the role of vaginal microbiota in VVC and related infectious diseases.