Treatment Of Fungal Infections Research Articles

The effectiveness and safety of posaconazole enteric-coated tablet versus oral suspension in invasive fungal infections.

Posaconazole enteric-coated tablet and oral suspension are two oral drugs in the treatment of invasive fungal infections (IFIs). This study compared the effectiveness and safety between posaconazole enteric-coated tablet and oral suspension, and provided a real world basis for the clinical practice. A retrospective cohort study was performed on IFIs patients treated with posaconazole enteric-coated tablet or oral suspension. The primary endpoints were in-hospital mortality, treatment discontinuation rate and clinical effective rate. The secondary endpoints were adverse events incidence (liver dysfunction, renal dysfunction and hypokalemia). One hundred and forty-four patients were totally included and divided into enteric-coated tablet group (n = 46) and oral suspension group (n = 98). There was no significant difference in effectiveness and safety between two groups. The female (OR = 0.130, P = 0.018) and diabetes mellitus (OR = 4.242, P = 0.003) were independently associated with combined in-hospital mortality/treatment discontinuation rate. The renal replacement therapy (OR = 10.071, P = 0.006), hypoalbuminemia (OR = 6.646, P = 0.002) and posaconazole duration (OR = 1.119, P = 0.002) were risk factors for liver dysfunction. The posaconazole enteric-coated tablet has comparable effectiveness and safety with oral suspension in IFIs, which need large-scale cases studies to confirm in the future.

Repurposing of Statins Against Superficial Fungal Infections

In a few decades fungal infections will become a major worldwide health concern. Research reveal that the fungal strain becomes resistant to current medications in cases of HIV infections, corona infections and environmental factors particularly in people with impaired immune systems. The amount of organ transplants and medication used for therapy all have contributed to an increase in the immunocompromised population. The fungal infections are becoming a more significant cause of mortality and morbidity. An estimated 1.5 million fatal consequences are caused by fungal pathogens annually. In a few decades, fungal infections will become a major worldwide health concern, so that unprecedented rates of fungal resistance to currently available antifungal medicines has been observed.The drug repurposing approaches lowers costs and time by investigating previously approved medicines with known safety and pharmacokinetics toxicity profile for novel therapeutic effects.The HMG – CoA reductase inhibitors drugs statins shows antifungal properties against tinea spp. group of common fungus that causes superficial infections. We have evaluated statins for their antifungal potential by insilico studies & Invitro studies & validate results with standard drugs itraconazole & ketoconazole.The docking studies shows highest binding energy shown by atorvastatin among all statin were used for docking studies pravastatin , atorvastatin, simavastatin ,fluvastatin & rosuvastatin . against fungal protein (PDB ID:5V5Z) & human protein (PDB ID: 3LD6) was found to be -13.52 &13.4 kcal/mole .The invitro studies shows MIC values for atorvastatin against Trichophyton rubrum , Microsporum canis & Epidermatophyton flocossum fungal strains found between 125 μg/ml to 150 125 μg/ml where as for standard drugs was found between 12.5 μg/ml to 25 μg/ml. Following insilico & invitro research atorvastatin determined and may be used for the treatment of fungal infections.

Exploring pharmacists’ understanding and use of antifungals at a tertiary hospital in England - an interview study

Abstract Introduction Antimicrobial resistance (AMR) is an emerging crisis worldwide. If continued, it is estimated AMR could cause over 10 million deaths annually by 20501. Antifungals are critical in the treatment and prophylaxis of fungal infections, especially invasive fungal infections which can be life-threatening. The national and international antimicrobial stewardship action plan focus primarily on the use of antibacterials. Antifungals have not yet been a focus for stewardship programmes. The appropriate use and understanding surrounding antifungals remain a challenge among healthcare professionals, including pharmacists but there is scarce empirical evidence to demonstrate this problem. Aim To explore pharmacists’ understanding and use of antifungals at a tertiary hospital in England. Methods A qualitative study utilising a constructivist approach involving one-to-one online semi-structured interview based on the Critical Incident Technique2 was conducted. Pharmacists working in the tertiary hospital were purposively sampled and recruited to participate in the study. Following informed consent, participants took part in a semi-structured interview via Microsoft Teams with a researcher. Interviews explored 1) the general purpose of using antifungals and 2) system factors and decisions taken when managing a routine and unusual or challenging case using antifungals. The interviews were audio-recorded and then transcribed verbatim. Transcripts were analysed using reflexive thematic analysis3. The study was registered with the tertiary hospital where participants were recruited from. This study was registered with Oxford University Hospitals NHS Foundation Trust (ref no. 8482) and received ethical approval from the University of Reading School of Chemistry, Food and Nutritional Sciences and Pharmacy internal ethics review committee (study no: 46/2023). Results Nine participants took part in the study. Interviews took an average of 29 minutes (range 15-55 minutes). Participants worked in different specialties including oncology, haematology, paediatrics, and respiratory care. Three themes were generated through the analysis. Theme 1: Diagnosing and managing fungal infections is complex. Limited and/or lack of reliable and timely diagnostic testing makes diagnosing fungal infections difficult. Consequently, patients were sometimes prescribed empiric antifungals to avoid treatment delay. Treatment was then reviewed once test results were available. Patient-related issues such as comorbidities and drug-drug interactions contribute to complex treatment plans. Theme 2: Antifungal stewardship involved a multidisciplinary approach. Pooling together expertise amongst healthcare professionals was imperative in decision-making. Pharmacists were often key antifungal stewards and medication experts despite working with uncertainty. Theme 3: Expressed need to upskill on antifungal stewardship. Participants were aware of gaps in their experience and knowledge when managing complex fungal infections. They want to be more confident in their role. Discussion/conclusions To our knowledge, this is the first study investigating hospital pharmacists’ understanding and use of antifungals in England. Our study showed that pharmacists navigate uncertainties when using antifungals. Pharmacists were viewed as antifungal stewards and medication experts in a multidisciplinary team but pharmacists were themselves aware that they need more exposure to a wider range of scenarios to enhance their confidence. Our findings suggest a need for reliable diagnostic-driven approaches and education and training initiatives for pharmacists to steward antifungals. Our participants worked in one tertiary hospital representing the culture and work practice specific to the hospital. It would be interesting to explore experiences of pharmacists working in other hospitals.

Construction and evaluation of transdermal delivery system of terbinafine-loaded plant exosomes for the treatment of cutaneous fungal infections

Local transdermal of antifungal agents is a problem that limits the effectiveness of clinical treatment of dermatomycosis. In this study, cucumber-derived plant extracellular vesicles (PEV) were extracted and loaded with the antifungal drug terbinafine (TBF) to form TBF-PEV, which was applied locally to the site of skin fungal infection to improve the transdermal transport capacity of TBF and the antifungal effect in vitro and in vivo. Chemical enhancer and physical enhancer methods were replaced by low immunogenicity and non-irritating PEV. TBF-PEV caused obvious curling and wrinkling in the skin, induced changes in the distribution of skin lipids, and changed the structure and content of skin lipids and proteins, thereby increasing the transdermal efficiency of TBF. The local drug concentration was increased, and the antifungal effect was improved in vitro and in vivo. It was first found that PEV inhibited the growth of Candida albicans with high efflux pump expression. In general, this paper has certain significance in local transdermal treatment of fungal skin infections and reversal of fungal resistance.

Development of a nanoemulsion containing Lippia origanoides essential oil with antifungal activity by low energy method: from extraction to formulation

The essential oil of Lippia origanoides is of great pharmacological interest because of a wide variety of attributes, in particular its antifungal action. Due to its low solubility in aqueous media, high volatility, and a high propensity for physicochemical degradation, the search for nanostructured systems to promote the stability of this phytocomplex is necessary. Nanoemulsion is an alternative method to stabilize and preserve this type of active ingredient, especially when generated by a low energy method and using Syagrus coronata (licuri) oil as an active carrier and stabilizer of this nanostructure. The objective of the present investigation was to formulate a stable nanoemulsion with Lippia origanoides essential oil carried through licuri oil with antifungal action by the low energy method. For this, we began with the extraction of the essential oil and the phytochemical characterization obtaining the chemotype B of this Lippia (carvacrol: 49.12%). Then, using the pseudoternary phase diagram, the optimal ratio of the oil phase 6:4 (essential oil: Syagrus coronata oil) was established, adding 15% of surfactant (polysorbate 80) and 75% of the aqueous phase. Then, with the formulated nanoemulsion, the physical-chemical characterization and evaluation of preliminary and accelerated stability were carried out. In addition, cytotoxicity, Franz cell permeation and antifungal activity against dermatophytes were evaluated. A stable nanoemulsion was obtained by the low energy method with the characteristic appearance of a nanoemulsion and a characteristic odor of essential oil. The average size of the nanoparticles was around 167.5 nm, narrow PDI (<0.2 nm), zeta potential below -10.0 mV, acidic pH (5.1), average conductivity 134.4 μSm/cm, refractive index characteristic of a translucent system and low viscosity (<6.0 mPa.S). Regarding cytotoxicity, it proved to be safe at dosages below 90 μg/mL, efficient in terms of permeation (76.7% in 24h) and effective in terms of antifungal activity as it had a minimum inhibitory concentration between 234.4/156.3 μg /mL and 11.2/7.5 μg/mL against the tested dermatophytes. In view of the results, a nanoemulsion containing the essential oil of L. origanoides carried by the oil of Syagrus coronata was shown to be a potential product for the topical treatment of fungal infections like dermatophytosis.

Crushed posaconazole delayed-release tablets for antifungal prophylaxis and treatment in children.

Therapeutic drug monitoring (TDM) is recommended for posaconazole to achieve target concentrations of ≥0.7 mg/L and ≥1.0 mg/L for prophylaxis and treatment of invasive fungal infection (IFI), respectively. However, target attainment is challenging with the oral suspension, particularly in children. Here, we describe our experience using crushed delayed-release tablet (DRT) in a paediatric cohort, with a focus on TDM. We undertook a retrospective audit of crushed posaconazole DRT administration via enteral feeding tubes (EFTs) for patients aged ≤18 years over 18 months at The Royal Children's Hospital Melbourne who had at least one trough concentration measured at steady state. Details of patient demographics, posaconazole dosing, monitoring and adverse effects were recorded. Twelve patients with a median age of 9 years (range 2 to 14) received posaconazole DRT via EFT for prophylaxis (n = 8) or treatment (n = 4). All children achieved target concentration, with a median dose of 7 mg/kg/day (range 5 to 11) for prophylaxis and 13 mg/kg/day (range 9 to 20) for treatment. The median time to reach therapeutic levels was 7 days (range 5 to 14) for prophylaxis and 20 days (range 15 to 35) for treatment. One child had blockage of their EFT, which was attributed to posaconazole. No other adverse effects were observed. Crushed posaconazole DRT administered via EFT may be used as a method of attaining therapeutic posaconazole concentrations in children for antifungal prophylaxis and treatment.

Current Updates on Pathogenesis, Systemic Therapy, and Treatment of Invasive Fungal Infections.

Numerous health hazards are associated with fungal infections, ranging from asymptomatic cases to potentially fatal invasive diseases that are especially dangerous for those with impaired immune systems. The main causes behind these diseases are opportunistic fungi, namely Aspergillus, Candida, and Cryptococcus. Invasive fungal infections (IFIs) require a global response that includes the development of vaccines, standardized protocols for diagnosis, potent antifungal medications, and strategies to stop drug-resistant strains. Improving high-risk group diagnosis and treatment is essential to lowering death rates. This review highlights the substantial health concerns associated with fungal infections, especially in immunocompromised individuals, and identifies Aspergillus, Candida, and Cryptococcus as the main pathogens. It highlights the necessity of international efforts, such as the development of novel diagnostic instruments, imaging methods, and antifungal drugs, to combat these invasive infections. The review also addresses the increasing need for novel treatment approaches in light of the developing resistance to widely used antifungal medications. Furthermore, the significance of secretory proteins in fungal pathogenicity and the potential of combination therapy are investigated. It is also suggested that a multimodal strategy be used to fight these illnesses, given the promise of multivalent vaccinations. Overall, this study emphasizes how critical it is to develop better diagnostic and treatment strategies in order to successfully control and lessen the impact of invasive fungal diseases on the health of the world.

Outcomes of Invasive Fungal Infections Treated with Isavuconazole: A Retrospective Review.

Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57-73% response rate). We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections.

Synthesis of kanamycin-azole hybrids and investigation of their antifungal activities

The World Health Organization (WHO) recognizes Candida albicans and Cryptococcus neoformans as the critical priority fungal pathogens for which therapeutic solutions are needed. Azole-based antifungal agents, including triazoles, diazoles, and thiazoles, are widely used in the treatments for fungal infections. In light of past successes in the transformation of antibacterial kanamycin into antifungal derivatives via chemical modifications, a new library of kanamycin-azole hybrids was synthesized and tested against a panel of azole-resistant and susceptible Candida and Cryptococcus strains. Structure activity relationship (SAR) studies revealed pivotal roles for antifungal activity of the azole ring (imidazole vs triazole) and halogen substituents on the benzene ring (F vs Cl). Most notably, hybrids 13, 14 and 15 were active against resistant C. albicans, C. tropicalis and C. neoformans strains and non-toxic towards mammalian cells. Mode of action investigations using fluorogenic dyes, (SYTOXTM) showed the fungal active compounds could permeabilize fungal membranes even at ¼ MICs. These findings reveal novel azole-based antifungals that could offer new therapeutic options for candidiasis and cryptococcosis.

Discovery of highly potent triazole derivatives with broad-spectrum antifungal activity based on Iodiconazole

The widespread use of broad-spectrum antibiotics, the growing number of immunocompromised individuals, and the emergence of drug-resistant strains have resulted in the increasing incidence and mortality of invasive fungal infections. Azole drugs are the primary treatment for invasive fungal infections, and Iodiconazole is a potent azole drug with strong antifungal activity, but its stability is poor. In order to improve stability, a series of triazole compounds containing ethynyl group were designed and synthesized. Most of the compounds showed strong inhibitory activity against pathogenic fungi, among which compound 20l showed excellent inhibitory activity against pathogenic fungi and drug-resistant fungi. Importantly, and the stability of 20l (T1/2 = 30.2 min) was obviously improved compared with Iodiconazole (T1/2 = 4.39 min). In addition, the preferred compound 20l can prevent fungal phase transition and the formation of fungal biofilm, and show satisfactory fungicidal activity. In addition, the compound 20l was almost non-toxic to mammalian HUVEC cell and 293T cell. In vivo pharmacokinetic studies showed that 20l had acceptable pharmacokinetic properties. These results strongly demonstrate that compound 20l was worth further investigation as a potential antifungal inhibitor.

Implementation of Antigen-Based Diagnostic Assays for Detection of Histoplasmosis and Cryptococcosis among Patients with Advanced HIV in Trinidad and Tobago: A Cross-Sectional Study.

The Caribbean continues to have high HIV prevalence globally with concurrently high mortality rates due to opportunistic Infections. This study addresses the prevalence of histoplasmosis and cryptococcosis among patients living with advanced HIV disease (AHD) in Trinidad and Tobago, focusing on the implementation of antigen-based diagnostic assays. Conducted as a cross-sectional survey across five HIV treatment sites, 199 participants with advanced HIV disease were enrolled between July 2022 and September 2023. Diagnostic testing was performed using the Clarus Histoplasma Galactomannan Enzyme Immunoassay (EIA), and the Immy CrAg® LFA Cryptococcal Antigen Lateral Flow Assay on urine and blood samples, respectively. Results revealed that 14.6% of participants were found to be co-infected with either histoplasmosis or cryptococcosis, with histoplasmosis being more prevalent (10.5%) than cryptococcosis (4.0%). The study found no significant demographic differences between newly diagnosed and previously diagnosed participants. However, a lower median CD4 count was associated with a higher risk of fungal opportunistic infections. The findings underscore the critical role of systematic use of fungal antigen-based diagnostic assays among patients with AHD to improve the timely diagnosis and treatment of fungal infections among people living with HIV in resource-limited settings and to improve patient outcomes and survival.

Identification of novel and potent triazoles targeting CYP51 for antifungal: Design, synthesis, and biological study

Invasive fungal infections (IFIs) are emerging as a serious infectious disease worldwide. Due to the lack of effective antifungal drugs and serious drug resistance, the number of people with low immunity is increasing, leading to high morbidity and mortality. Azole drugs targeting CYP51 are widely used in the treatment of invasive fungal infections. By analyzing representative azole antifungal drugs, the characteristics of pharmacophore were summarized. The binding mode of lead compound Iodiconazole was analyzed, and it was found that the narrow hydrophobic cavity was not fully occupied. Therefore, a series of triazole compounds were designed and synthesized by fragment growth strategy. Most of the compounds showed strong inhibitory activity against pathogenic fungi, among which compound A33 showed excellent inhibitory activity against pathogenic fungi and drug-resistant strains. In addition, the preferred compound A33 can prevent fungal phase transition, the formation of fungal biofilm, and show satisfactory fungicidal activity. In addition, the compound A33 was almost non-toxic to mammalian HUVEC cell. These results strongly suggested that compound A33 was worth further investigation as a potential azole inhibitor.

Surgical treatment of invasive pulmonary fungal infections in immunocompromised pediatric patients: Aspergillus spp. and other emerging fungi.

Invasive Pulmonary Fungal Infections (IPFIs) represent a diagnostic and therapeutic challenge. The exact role of surgery is not well defined. This study analyzes our experience with surgical treatment of IPFI in immunocompromised pediatric patients and, secondarily, compares IPFI caused by Aspergillus spp. with other fungal infections. This is a retrospective review (2000-2019) of patients with IPFI surgically treated at our pediatric institution. Statistical analysis was used to compare data between Aspergillus spp. and non-Aspergillus IPFI. Twenty-five patients (64% female) underwent 29 lung resections. Median age at surgery was 7.19years (1.63-19.14). The most frequent underlying condition (64%) was acute leukemia. Surgical indications included persistence or worsening of symptoms and pathological image findings (52%) or asymptomatic suspicious lesions in patients scheduled for intensive cytotoxic treatments or hematopoietic stem cell transplantation (48%). All patients underwent atypical lung resections, except one lobectomy. Aspergillus spp. was the most frequently isolated pathogen (68%). Follow-up was 4.07years (0.07-18.07). Surgery-related mortality was 0%, but 4 patients died in the 100days following surgery (2 due to disseminated fungal infection); the remaining 21 did not show signs of IPFI recurrence. Non-specific consolidations on CT scan were more frequent in non-Aspergillus IPFI (p < 0.05). Surgical treatment of IPFI should be considered as a part of the treatment in selected pediatric immunocompromised patients, and it may have both diagnostic and therapeutic advantages over non-surgical management. When there is clinical suspicion of IPFI but CT scan shows unspecific alterations, the possibility of a non-Aspergillus IPFI should be considered.

Isavuconazole off-label use as an empirical treatment of invasive fungal infections

Given its good tolerance and broad spectrum, isavuconazole is increasingly used off-label as an empirical therapy of invasive fungal infections. We retrospectively reviewed isavuconazole empirical treatment during a 12-month period in four hospitals. During isavuconazole treatment (n=27), none of the patients had a mycological evidence for fungal infection, but 19% (5/27) developed liver test abnormalities without leading to isavuconazole discontinuation. Isavuconazole could be considered as an off-label empirical therapy only if patients cannot receive caspofungin or liposomal amphotericin B.

The Endocytosis Adaptor Sla1 Facilitates Drug Susceptibility and Fungal Pathogenesis Through Sla1-Efg1 Regulating System in Candida albicans.

The role of endocytosis in Candida albicans drug-resistance and pathogenicity remains poorly understood, despite its importance as a fundamental component of intracellular trafficking. In order to understand the role of endocytosis in Candida albicans cell wall integrity, drug resistance, and virulence. Detection of intracellular endocytosis by FM4-64 staining; Scanning electron microscopy is used to detect cell wall components; Spot assay for detecting drug sensitivity; Co-ip is used to detect protein interactions. In this study, we found the functions of Sla1 in regulating endocytosis is conserved among pathogenic fungi. Our results also revealed that the deletion of the SLA1 gene altered cell wall properties, composition, and gene expression. In addition, we showed that C. albicans Sla1 was responsible for hyphal development in vitro and for fungal pathogenicity in a murine infection model. Intriguingly, sla1∆/∆ mutant demonstrated enhanced drug resistance, and Sla1 was found to interact with the transcription factor Efg1; the relationship between Sla1 and Efg1 impacts the expression of genes encoding components of the ergosterol biosynthesis pathway, including ERG1, EGR11, and ERG25. These findings have expanded our knowledge of the capabilities of Sla1 beyond its role as an endocytosis adapter and provided insights into a potential new therapeutic target for the treatment of fungal infections.

Strengthening Fungal Infection Diagnosis and Treatment: An In-depth Analysis of Capabilities in Honduras.

Invasive fungal infections (IFIs) are a major public health concern in low- and middle-income countries (LMICs) due to limited diagnostic and treatment resources, leading to high morbidity and mortality. Despite their significant global burden, IFIs are underrecognized and underdiagnosed in LMICs. This study evaluates the diagnostic and therapeutic capacities for managing IFI in Honduras, a country with unique health care challenges. From March to December 2023, a comprehensive survey was conducted across multiple health care centers in Honduras. The survey, reviewed for content and clarity by local medical institutions, targeted medical microbiologists and clinicians to assess various aspects of fungal disease diagnosis and treatment. Data included the availability and use of diagnostic tools and antifungal therapies, identifying gaps and limitations in current practices. The survey revealed that Candida spp (97.4%) and Aspergillus spp (35.9%) were the most concerning pathogens. Although microscopy and culture methods were available in most institutions, their application in suspected IFI cases was inconsistent, and antifungal susceptibility testing was rarely performed. Advanced diagnostic techniques, such as antigen detection, were available in only a few institutions, while antibody detection and polymerase chain reaction testing were entirely absent. All hospitals had access to at least 1 triazole antifungal, typically fluconazole, but there was a notable scarcity of more potent antifungals, including amphotericin B formulations and echinocandins. The limited use of available diagnostic tools and the restricted availability of essential antifungals were identified as major barriers to effective IFI management. This study highlights significant gaps in the diagnostic and therapeutic capabilities for managing IFI in Honduras. The underutilization of basic diagnostic tools, the inaccessibility of advanced testing methods, and the limited availability of essential antifungal medications underscore the urgent need for capacity-building initiatives, infrastructure improvements, and policy reforms. Addressing these deficiencies is critical for enhancing the management of IFI in Honduras, with broader implications for similar LMIC settings. These findings can inform targeted interventions and resource allocation to improve outcomes for patients with IFI.

Formulation Development, Evaluation and Anticandidal Screening of Herbal Cream of Trianthema portulacastrum Linn.

Trianthema portulacastrum, commonly known as black pigweed (E) and patharchata (H) belongs to the family Lamiaceae is a flowering medicinal pants. The plant contains various bioactive compounds such as trianthenol, leptormol, cinnamic acid, beta cyanin and ecdysterone. Traditionally, almost every part of the plant is used for the treatment of inflammation, fungal infection, pain, liver disorders, etc. In the present study, hydroalcoholic extract of leaves of Trianthema portulacastrum was taken to formulate herbal cream in three different batches, i.e., C-I, C-II and C-III, using different concentrations of the extract and prepared cream. Also, the anti-candidal activity of the herbal cream was determined in the fungus Candida albicans. The results obtained indicated that the herbal cream containing hydroalcoholic extract of the selected plant possesses significant anti-candidal activity and hence it may used in the treatment of fungal infection.

Adhesin Antibody-Grafted Mesoporous Silica Nanoparticles Suppress Immune Escape for Treatment of Fungal Systemic Infection.

Life-threatening systemic fungal infections caused by Candida albicans are significant contributors to clinical mortality, particularly among cancer patients and immunosuppressed individuals. The evasion of the immune response facilitated by fungal surface components enables fungal pathogens to evade macrophage attacks and to establish successful infections. This study developed a mesoporous silica nanoplatform, i.e., MSNP-EAP1Ab, which is composed of mesoporous silica nanoparticles grafted with the antibody of C. albicans surface adhesin Eap1. The activity of MSNP-EAP1Ab against C. albicans immune escape and infection was then evaluated by using the cell interaction model and the mouse systemic infection model. During interaction between C. albicans cells and macrophages, MSNP-EAP1Ab significantly inhibited fungal immune escape, leading to the enhanced phagocytosis of fungal cells by macrophages, with phagocytosis rates increasing from less than 8% to 14%. Furthermore, after treatment of the C. albicans-infected mice, MSNP-EAP1Ab drastically prolonged the mouse survival time and decreased the kidney fungal burden from >30,0000 CFU/g kidney to <100 CFU/g kidney, indicating the rapid recognition and killing of the pathogens by immune cells. Moreover, MSNP-EAP1Ab attenuated kidney tissue inflammation, with remarkable attenuation of renal immune cell accumulation. This study presents an innovative nanoplatform that targets the C. albicans adhesin, offering a promising approach for combatting systemic fungal infections.

Formulation Development of Mucoadhesive Vaginal Gel of Secnidazole and Voriconazole.

Purpose: Over the preceding decades, developing conventional drug delivery in to modified form has acquired importance in the pharmaceutical industry. Vaginal drug delivery system offers localized drug administration of drug and also avoids unwanted side effects of oral drug delivery. Vaginal drug delivery system has significant role in medical practice. Even though VDDS has a lot of advantages over the other routes of administration. The goal of developing the Mucoadhesive Vaginal Gel was to achieve the synergistic effect of voriconazole and secnidazole in the treatment of bacterial and fungal vaginal infections. Method: Mucoadhesive antimicrobial vaginal gel was optimised using Design expert software using Carbopol 934, HPMC K4M polymers. Result: Formulation was evaluated for various rheological parameters ,antimicrobial activity, invitro drug release and stability study. The spreadability and pH was found to be 5.5 to 7.4 cm and 4.12. Its compatible with vaginal pH. The selected optimized F8 formulation is the best formulation and the drug ratio is 2:1. and optimum gel viscosity is 1874 cps. antimicrobial study revealed that faster drug release of test formulation was compared to marketed product. It indicates as inhibition zone. Conclusion: The combination of drugs can serves as better option for treating vaginitis, compared to single drug formulation. Mucoadesion increases contact time of drug with affected area which rendered formulation more effective.

Development and Evaluation of Voriconazole Loaded Invasomes Gel for Enhanced Antifungal Activity.

Although it has limited solubility and poor permeability to the skin, voriconazole (VRC) is a viable choice for the topical treatment of fungal infections. Owing to these constraints, treating the inflection requires several injections over an extended period. The goal of this work was to produce a VRC invasome gel with improved topical antifungal activity. The Box-Behnken design (BBD) program was utilized to optimize the IVS after it was created using the thin-film hydration process. The optimized invasome formulation through BBD has 159.9 nm of vesicle size, 68.58% of entrapment efficiency, and 23.5 mV of zeta potential. The spherical shape of the vesicle was revealed using scanning microscopy. According to FTIR spectra, the medication and polymers do not interact. The optimized invasomal VRC gel exhibited an optimum of 345 to 589 cp. Ex-vivo permeation studies of IG4 exhibited a higher flux of 0.168 as compared to pure voriconazole. An antimicrobial study was accepted to check the antimicrobial efficiency of voriconazole gel (IG4). The study confirmed a good zone of inhibition of the fungus infection (C. albicans). The voriconazole invasome’s potential diffusion and antibacterial efficacy are demonstrated here. Invasomal gel was found to be an effective carrier and a desirable strategy for improving the topical distribution of VRC to treat fungal infections.