To provide a comprehensive summary of a decade (2014-2025) of high-quality research from Q1-Q3 journals on formulation development and improved drug-delivery methods for vulvovaginal candidiasis, addressing the limits of conventional antifungal therapy. A detailed narrative review was carried out using PubMed, Scopus, Springer, Wiley, Frontiers, ClinicalTrials.gov, and Google Scholar. To maintain scientific rigor, only the most relevant Q1-Q3 indexed publications were included. Studies published in the last eleven years have been evaluated for their relevance to vaginal drug delivery systems and anti-fungal formulations. Data were systematically retrieved and described in text and tables, with 203 formulation techniques given, including nanoparticles, vesicular carriers, mucoadhesive systems, thermosensitive gels, electrospun nanofibers, microneedles, and three-dimensional printed dosage forms. The key outcomes examined were vaginal retention, drug release behavior, mucosal penetration, antibiofilm activity, and antifungal efficacy. In comparison to conventional formulations, advanced drug-delivery systems displayed longer vaginal residence time, sustained drug release, and improved tissue penetration. Nanoparticle-based and mucoadhesive systems demonstrated increased antifungal effectiveness against both microbial and biofilm-associated Candida species, with absolute fungal clearance improvements ranging from 25 to 45% in preclinical applications. This review combines eleven years of formulation research, minimizing the need for readers to sift over fragmented literature. Major limitations included study design variability and a lack of long-term clinical data. This 11-year synthesis identifies improved drug-delivery technologies as promising patient-centered solutions for overcoming resistance, recurrence, and poor drug retention in VVC treatment. These drug delivery systems constitute an important step toward next-generation antifungal therapy and better clinical outcomes.

Acute generalized exanthematous pustulosis (AGEP) is a rare, severe type IV hypersensitivity reaction, most commonly triggered by antibiotics, calcium channel blockers, or antifungal agents, while fluconazole-induced AGEP is exceptionally reported. Early recognition and prompt management are essential to prevent complications. We report the case of a 21-year-old female with no personal or family history of psoriasis who developed a sudden-onset, pruritic, erythematous pustular rash six days after a single 150 mg dose of fluconazole prescribed for vaginal candidiasis. On examination, she was febrile (39°C) and asthenic, with widespread non-follicular pustules initially involving intertriginous areas and subsequently extending to the trunk and limbs. The Nikolsky sign was negative, and mucosal surfaces were spared. Laboratory investigations revealed leukocytosis (10,400/mm[3]) with neutrophilia (7,800/mm[3]), and pustular cultures were sterile. Histopathological examination showed intraepidermal pustules associated with dermal neutrophilic and eosinophilic infiltrates. The European Study of Severe Cutaneous Adverse Reactions (EuroSCAR) score was 11, confirming the diagnosis of fluconazole-induced AGEP. Rapid clinical improvement was observed following discontinuation of fluconazole and supportive treatment with antihistamines and emollients; desquamation occurred within four days, and no systemic complications were noted. Although rare, fluconazole should be considered a potential cause of AGEP, and early diagnosis with prompt withdrawal of the offending drug remains essential to ensure a favorable prognosis.

This study evaluated the hemolytic activity of Candida albicans isolates from the female reproductive tract and investigated the in vitro effects of quinalizarin on fungal growth, hemolysis, and ECE1 expression. Ninety-four clinical C. albicans isolates and three ATCC reference strains were analyzed. Hemolytic activity was quantified in culture supernatants and normalized per 10[7] cells. Antifungal susceptibility and the effect of quinalizarin on hemolysis were assessed using broth microdilution and hemolysis assays. Expression of the ECE1 gene was evaluated by quantitative real-time PCR in three selected hemolytic strains. Drug interactions between quinalizarin and fluconazole were determined using the fractional inhibitory concentration index (FICI). Among the 97 tested strains, 78 exhibited hemolytic activity with variable intensity. Quinalizarin demonstrated antifungal activity, with MIC values ranging from 2 µg/mL to 256 µg/mL, and showed synergistic effects with fluconazole in selected strains. Exposure to quinalizarin at subinhibitory concentrations reduced ECE1 transcript levels to 22.8-73.6% of controls (p < 0.05) in the analyzed strains. However, the phenotypic effect on hemolysis was limited, with residual activity remaining high: 82% (p < 0.05), 93.7% (p < 0.05), and 83% (p < 0.05) relative to untreated controls in C. albicans ATCC 10231, ATCC 90028, and a clinical isolate, respectively. FICI analysis confirmed synergistic interactions between quinalizarin and fluconazole. This preliminary in vitro study highlights the need for further investigation into the relationship between ECE1 expression, candidalysin-mediated damage, and the antifungal potential of quinalizarin.

Vulvovaginal candidiasis (VVC) is a prevalent mucosal infection predominantly caused by Candida albicans (C. albicans). Vaginal lactobacilli contribute to colonization resistance and epithelial barrier integrity. However, therapeutic options remain limited and recurrence is common. In this study, we investigated the effects of a lactic acid bacteria mixture (LM; InoRexyne[®]) enriched with Lactiplantibacillus plantarum YC225 on antifungal activity and inflammation in vitro and in an estrogenized murine VVC model. In RAW264.7 macrophages and VK2/E6E7 vaginal epithelial cells, the LM cell-free supernatant inhibited C. albicans growth and reduced inflammatory readouts induced by lipopolysaccharide or C. albicans. In vivo, oral LM administration for 14 d attenuated VVC-associated histopathological damage, reduced vaginal IL-6 and nitric oxide levels, and decreased fungal burden compared with infected controls. LM also increased the expression of the tight junction marker gene Tjp1 and modulated inflammatory gene expression in vaginal tissue (NanoString panel), including downregulation of selected pro-inflammatory pathways and upregulation of the anti-fibrotic regulator Smad7. 16S rRNA profiling of fecal samples showed LM-associated shifts in gut microbial composition, including increased abundance of Lactobacillus/L. plantarum and decreased abundance of several opportunistic taxa. Correlation analysis suggested associations between specific gut taxa and VVC parameters. Collectively, these findings indicate that oral LM may mitigate VVC-associated inflammation, epithelial damage, and fungal burden, and these effects are accompanied by changes in gut microbiota composition.

Chondroitin sulfate (CS) is a glycosaminoglycan with various biological functions including antioxidant and anti-inflammatory effects. Candida species, particularly Candida albicans, are major pathogens involved in vulvovaginal candidiasis (VVC), which affects a majority of women, and novel antifungal agents are needed due to the limitations of current treatments. This study evaluated the antifungal efficacy of microbial chondroitin sulfate (MCS), produced via recombinant Escherichia coli (C2987), in a rat model of VVC. MCS was biosynthesized via the pETM6-PACF-vgb[+] plasmid harboring the kfoA, kfoC, kfoF, and vgb genes, and its structural integrity and composition were confirmed via NMR, HPLC, and FT-IR. VVC was induced in immunosuppressed, estrogen-treated Wistar albino rats, which were randomized into eight groups: uninoculated control, infected untreated control, cream base, nystatin, fenticonazole, and MCS at 0.1%, 0.5%, and 1.0%, respectively. Topical treatments were applied for seven days, and the vaginal fungal burden [colony-forming units (CFU)], the levels of cytokines (IL-4, IL-8, and IL-17), the levels of oxidative stress markers in rat serum [malondialdehyde (MDA) and superoxide dismutase (SOD)], and histopathology were assessed. MCS was associated with a dose-dependent reduction in fungal burden, with 1.0% MCS achieving CFU reductions comparable to those of nystatin and fenticonazole. Significant decreases in IL-8 and IL-17 and a moderate reduction in IL-4 were detected in rat vaginal lavage fluid, indicating an anti-inflammatory shift. Histopathological examination indicated qualitative differences in epithelial architecture and inflammatory cell distribution in the 0.5% and 1.0% MCS groups; however, inflammation scores did not reach statistical significance. Serum oxidative stress analysis revealed trends toward lower MDA levels and higher SOD activity, but the differences were not statistically significant. These findings suggest that MCS is a promising nonanimal-derived topical antifungal agent with both antifungal and immunomodulatory potential, warranting further clinical investigation.

Vulvovaginal candidiasis (VVC) is a highly prevalent fungal vaginal infection with a substantial impact on women's quality of life. Increasing evidence indicates that VVC pathogenesis is driven not only by high fungal burden but also by dysregulated host-immune responses, highlighting the need for therapeutic strategies that extend beyond conventional antifungal treatment.

Candida albicans is the primary etiological agent of acute vulvovaginal candidiasis (AVVC) and its recurrent form (RVVC), conditions that differ in clinical presentation, inflammatory context, and response to antifungal therapy. Although virulence factors and antifungal resistance have been individually linked to disease severity, their integrated contribution to distinct clinical outcomes remains poorly defined. Here, we performed a comprehensive phenotypic characterization of 58 clinical C. albicans isolates recovered from women with AVVC (n = 25) or RVVC (n = 33), and C. albicans SC5314 was included for comparison. We assessed fungal dimorphism, cell surface hydrophobicity, biofilm-forming capacity (BFC), and the production of secreted aspartyl proteinases (SAP) and lipases (LIP). Antifungal susceptibility to azoles and other clinically relevant agents was determined using an automated system. Multivariate unsupervised analyses were applied to identify integrated virulence phenotypes. All clinical isolates exhibited efficient filamentation. AVVC isolates displayed enhanced adherence, biofilm metabolic activity, and LIP production, whereas RVVC isolates exhibited increased SAP activity and reduced BFC. Unsupervised clustering and UMAP analysis identified four virulence clusters, including profiles specifically associated with AVVC or RVVC, as well as mixed phenotypes. Notably, a high prevalence of azole resistance was observed in both groups, with resistance patterns aligning with specific virulence clusters. Collectively, these findings indicate that AVVC and RVVC are associated with distinct, niche-adapted C. albicans virulence programs that integrate enzymatic activity, biofilm traits, and antifungal resistance. This structured phenotypic heterogeneity provides a framework to reinterpret vulvovaginal candidiasis as a multifactorial and adaptive process with important implications for disease persistence and therapeutic failure.

Vulvovaginal candidiasis (VVC) represents a global health issue. However, epidemiological data on VVC in eastern China are scarce, limited, and outdated. To address this gap, we conducted a six-year retrospective study (2019-2024), investigating the epidemiological characteristics, species distribution, and antifungal susceptibility patterns of VVC patients in Shanghai, China. VVC was confirmed based on clinical symptoms combined with laboratory examination. Candida species were identified by MALDI-TOF MS, and in vitro antifungal susceptibility testing (AFST) was carried out using the ATB FUNGUS 3 method. The epidemiological changes over time were analyzed using the χ2 test for trend. In total, 7,894 VVC episodes were identified among 7,167 individuals. Of these, 39 patients (0.54%) exhibited mixed Candida infections. Candida albicans was the predominant species (77.26%), followed by Candida glabrata (17.63%), Candida parapsilosis (1.53%), Candida tropicalis (1.17%), and Candida krusei (1.00%). Other species were rare, each accounting for less than 1.0%. VVC shows high prevalence in our region, with C. albicans as the most prevalent pathogen, followed by C. glabrata. And an increasing trend in C. glabrata VVC was observed, accompanied by consistently high rates of voriconazole resistance. Fluconazole resistance was observed in 18.82% of C. albicans with cross-resistance to other azoles. Thus, our findings highlight the significance of Candida species identification and accurate diagnosis in VVC, underscoring the necessity for targeted antifungal management.

Recurrent vulvovaginal candidiasis (RVVC) affects 5-8% of women of reproductive age. Host genetic factors, particularly single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs), may influence RVVC susceptibility by impairing vaginal mucosal antifungal immunity. The aim of this study was to assess the effect of SNPs in genes encoding TLRs on RVVC susceptibility. Τhe distribution of TLR2 Arg753Gln and TLR4 Asp299Gly/Thr399Ile polymorphisms in Greek women, including RVVC (n = 63), first-episode VVC (n = 37), Gardnerella vaginalis vaginitis (GV, n = 36) patients, and healthy controls (n = 61), was investigated using TaqMan SNP genotyping. Genotype and allele frequencies were analyzed under allelic and dominant models, with odds ratios (ORs), 95% confidence intervals (CIs), and linkage disequilibrium assessed. TLR4 Asp299Gly and Thr399Ile heterozygotes were significantly more frequent in RVVC patients compared with controls and affected RVVC susceptibility (OR: 5.57, 95% CI: 1.17-26.56, p: 0.0172; OR: 4.92, 95% CI: 1.02-23.78, p: 0.0306, respectively). No associations were observed for TLR2 Arg753Gln or for any SNP with GV or first-episode VVC. TLR4 variants co-segregated, indicating a haplotype effect. TLR4 haplotypes, rather than TLR2 polymorphism, confer increased RVVC susceptibility, supporting a genetically distinct, mucosal immunity-driven pathogenesis. Larger, ethnically diverse studies with functional assays are warranted to validate these findings and guide personalized prevention and treatment strategies.

Atopic dermatitis (AD) is frequently associated with epidermal barrier dysfunction and may be complicated by recurrent infections. We report a 31-year-old Han Chinese woman with lifelong ichthyosis vulgaris and severe AD, complicated by recurrent vaginal Nakaseomyces glabratus (N. glabrata) infection and herpes simplex virus type 1 (HSV-1) reactivation. Antifungal susceptibility testing demonstrated reduced susceptibility to multiple azole agents. Whole-exome sequencing identified a heterozygous FLG frameshift mutation (c.3321delA) together with heterozygous variants in TNFRSF13B, MPO, and DOCK8, all confirmed by Sanger sequencing. At follow-up, mucocutaneous infections improved, while cutaneous manifestations persisted under topical management. This case highlights the potential combined contribution of epidermal barrier defects and immune-related gene variants to complex atopic disease with recurrent infections.