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3 Biotech Jul 2023The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered... (Review)
Review
The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera , , and . There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.
PubMed: 37309405
DOI: 10.1007/s13205-023-03648-2 -
Journal of Obstetrics and Gynaecology :... Dec 2023At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a... (Review)
Review
At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a microsomal cytochrome P450 (CYP) enzyme. Imidazoles and triazoles impair the biosynthesis of ergosterol for the cytoplasmic membrane and lead to the accumulation of 14-α-methyl sterols. The synthetic imidazole miconazole is additionally able to increase intracellular reactive oxygen species, at least in part through inhibition of fungal catalase and peroxidase. This unique feature of miconazole is probably the basis for its fungicidal activity in , in addition to the fungistatic mode of action. Studies show that miconazole is superior to nystatin treatment and demonstrate its impact as one of the best options in managing vulvovaginal candidiasis. Regarding recurrent vulvovaginal candidiasis, several new drugs are currently developed to ensure effective treatment also for this group of patients.
Topics: Female; Humans; Miconazole; Candidiasis, Vulvovaginal; Antifungal Agents; Imidazoles; Nystatin; Candida albicans; Cytochrome P-450 Enzyme System
PubMed: 37029724
DOI: 10.1080/01443615.2023.2195001 -
Acta Crystallographica. Section E,... Feb 2024The crystal structure of the new triclinic polymorph of miconazole {MIC; CHClNO; systematic name:...
The crystal structure of the new triclinic polymorph of miconazole {MIC; CHClNO; systematic name: ()-1-[2-(2,4-di-chloro-benz-yloxy)-2-(2,4-di-chloro-phen-yl)eth-yl]-1-imidazole} is reported and compared with the monoclinic form of solvent-free miconazole previously reported [Kaspiaruk & Chęcińska (2022 ▸). C, 343-350]. A comparison shows a different orientation of imidazole and one di-chloro-phenyl ring between polymorphic mol-ecules. In the crystal structure of the title compound, only weak halogen bonds and C-H⋯π(arene) inter-actions are found. Hirshfeld surface analysis and energy framework calculations complement the comparison of the two polymorphic forms of the miconazole drug.
PubMed: 38333136
DOI: 10.1107/S2056989024000276 -
The Journal of Antibiotics May 2024Antibiotic resistance is a major health problem worldwide. Pseudomonas aeruginosa is a Gram-negative pathogen with an arsenal of virulence factors and elevated...
Antibiotic resistance is a major health problem worldwide. Pseudomonas aeruginosa is a Gram-negative pathogen with an arsenal of virulence factors and elevated antimicrobial resistance. It is a leading cause of nosocomial infections with high morbidity and mortality. The significant time and effort required to develop new antibiotics can be circumvented using alternative therapeutic strategies, including anti-virulence targets. This study aimed to investigate the anti-virulence activity of the FDA-approved drugs miconazole and phenothiazine against P. aeruginosa. The phenotypic effect of sub-inhibitory concentrations of miconazole and phenothiazine on biofilm, pyocyanin, protease, rhamnolipid and hemolysin activities in PAO1 strain was examined. qRT-PCR was used to assess the effect of drugs on quorum-sensing genes that regulate virulence. Further, the anti-virulence potential of miconazole and phenothiazine was evaluated in silico and in vivo. Miconazole showed significant inhibition of Pseudomonas virulence by reducing biofilm-formation approximately 45-48%, hemolytic-activity by 59%, pyocyanin-production by 47-49%, rhamnolipid-activity by approximately 42-47% and protease activity by 36-40%. While, phenothiazine showed lower anti-virulence activity, it inhibited biofilm (31-35%), pyocyanin (37-39%), protease (32-40%), rhamnolipid (35-40%) and hemolytic activity (47-56%). Similarly, there was significantly reduced expression of RhlR, PqsR, LasI and LasR following treatment with miconazole, but less so with phenothiazine. In-silico analysis revealed that miconazole had higher binding affinity than phenothiazine to LasR, RhlR, and PqsR QS-proteins. Furthermore, there was 100% survival in mice injected with PAO1 treated with miconazole. In conclusion, miconazole and phenothiazine are promising anti-virulence agents for P. aeruginosa.
PubMed: 38724627
DOI: 10.1038/s41429-024-00731-5 -
International Journal of Molecular... May 2024Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new...
Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)AgNO], [(MTZ)Ag]SO, [Ag(MCZ)NO], [Ag(MCZ)BF], [Ag(MCZ)SbF] and [Ag(MCZ)ClO] (MTZ-metronidazole; MCZ-miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC values against the A375 line were demonstrated by [Ag(MCZ)NO] and [(MTZ)AgNO]. The compound [(MTZ)AgNO] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.
Topics: Humans; Melanoma; Miconazole; Silver; Antineoplastic Agents; Metronidazole; Cell Line, Tumor; Coordination Complexes; Cell Survival; Skin Neoplasms
PubMed: 38791121
DOI: 10.3390/ijms25105081 -
Heliyon Aug 2023Due to the adverse effects associated with long-term administration of antifungal drugs used for treating dermatophytic lesions like tinea unguium, there is a critical... (Review)
Review
Due to the adverse effects associated with long-term administration of antifungal drugs used for treating dermatophytic lesions like tinea unguium, there is a critical need for novel antifungal therapies that exhibit improved absorption and minimal adverse effects. Nanoformulations offer a promising solution in this regard. Topical formulations may penetrate the upper layers of the skin, such as the stratum corneum, and release an appropriate amount of drugs in therapeutic quantities. Liposomes, particularly nanosized ones, used as topical medication delivery systems for the skin, may have various roles depending on their size, lipid and cholesterol content, ingredient percentage, lamellarity, and surface charge. Liposomes can enhance permeability through the stratum corneum, minimize systemic effects due to their localizing properties, and overcome various challenges in cutaneous drug delivery. Antifungal medications encapsulated in liposomes, including fluconazole, ketoconazole, croconazole, econazole, terbinafine hydrochloride, tolnaftate, and miconazole, have demonstrated improved skin penetration and localization. This review discusses the traditional treatment of dermatophytes and liposomal formulations. Additionally, promising liposomal formulations that may soon be available in the market are introduced. The objective of this review is to provide a comprehensive understanding of dermatophyte infections and the role of liposomes in enhancing treatment.
PubMed: 37583758
DOI: 10.1016/j.heliyon.2023.e18960 -
Pharmaceutical Nanotechnology 2024Among the various prominent fungal infections, superficial ones are widespread. A large number of antifungal agents and their formulations for topical use are... (Review)
Review
Among the various prominent fungal infections, superficial ones are widespread. A large number of antifungal agents and their formulations for topical use are commercially available. They have some pharmacokinetic limitations which cannot be retracted by conventional delivery systems. While nanoformulations composed of lipidic and polymeric nanoparticles have the potential to overcome the limitations of conventional systems. The broad spectrum category of antifungals i.e. azoles (ketoconazole, voriconazole, econazole, miconazole, etc.) nanoparticles have been designed, prepared and their pharmacokinetic and pharmacodynamic profile was established. This review briefly elaborates on the types of nano-based topical drug delivery systems and portrays their advantages for researchers in the related field to benefit the available antifungal therapeutics.
Topics: Antifungal Agents; Humans; Animals; Administration, Topical; Nanoparticles; Nanotechnology; Drug Delivery Systems; Drug Carriers; Nanoparticle Drug Delivery System; Mycoses
PubMed: 37594096
DOI: 10.2174/2211738511666230818125031 -
Clinical Drug Investigation Jul 2023Naftifine, an allylamine, is highly effective against tinea pedis and exhibits relatively greater affinity to skin and nail beds, possibly due to its high lipophilicity.... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Naftifine Hydrochloride 2% Gel in Interdigital Tinea Pedis: A Phase III Randomised, Double-Blind, Parallel-Group, Active-Controlled Study in Indian Adult Patients.
BACKGROUND AND OBJECTIVE
Naftifine, an allylamine, is highly effective against tinea pedis and exhibits relatively greater affinity to skin and nail beds, possibly due to its high lipophilicity. To study the efficacy and safety of naftifine 2% gel in an Indian population, a phase III multicentre double-blind, comparative, parallel-group study was conducted in comparison with miconazole 2% gel in patients with interdigital tinea pedis, with mild to moderate symptoms.
PATIENTS AND METHODS
Patients presenting with mild to moderate signs and symptoms of interdigital tinea pedis and mycologically confirmed tinea infection were randomised to either naftifine hydrochloride 2% gel (n = 112) or miconazole 2% gel (n = 112) in 1:1 ratio. All patients were treated for 2 weeks with a follow-up of up to 12 weeks. Study evaluations were done at the end of 2, 6, and 12 weeks. The primary efficacy endpoint was the proportion of patients achieving clinical cure at week 6 (± 4 days) and secondary endpoints were the mycological cure at week 6 and week 12 and complete cure at week 12.
RESULTS
At the end of week 6, clinical cure was 54.55% and 50.00% in the naftifine and miconazole groups (p = 0.4960), respectively, and it was increased to 78.18% and 76.36% in the naftifine and miconazole group (p = 0.7455) at the end of week 12. Mycological and clinical cure were similar in the naftifine and miconazole groups at week 6 and week 12. The safety and tolerability profiles of both treatments were similar.
CONCLUSIONS
Naftifine 2% gel was efficacious and safe for the treatment of mild to moderate interdigital tinea pedis. Its clinical effectiveness was comparable to that of miconazole 2% gel.
TRIAL REGISTRATION
Clinical Trials Registry of India: CTRI/2021/01/030753.
Topics: Humans; Adult; Tinea Pedis; Antifungal Agents; Miconazole; Administration, Cutaneous; Treatment Outcome; Double-Blind Method
PubMed: 37462803
DOI: 10.1007/s40261-023-01288-1 -
European Journal of Pharmaceutical... Sep 2023Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy...
Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy of the vulvovaginal candidiasis (VVC). They were synthesized by emulsification and solvent evaporation techniques, characterized by diameter, polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy (AFM), evaluated in terms of efficacy against C. albicans in vitro, and tested in a murine VVC model. Nanoparticles showed 211nm of diameter with a 0.32 polydispersity index, -53mV of zeta potential, and 90% miconazole encapsulation efficiency. AFM evidenced nanoparticles with a spherical shape. They inhibited the proliferation of C. albicans in vitro and in vivo after a single administration. Nanoparticles released the miconazole directly in the site of action at low therapeutic doses, which was enough to eliminate the fungal burden in the murine VVC model. These systems were rationally designed since the existence of the HA induces their adhesion on the vaginal mucus and their internalization via CD44 receptors, inhibiting the C. albicans. Therefore, miconazole-loaded nanoparticles/HA represent an innovative non-conventional pharmaceutical dosage form to treat the VVC and recurrent VVC.
Topics: Humans; Female; Mice; Animals; Miconazole; Candidiasis, Vulvovaginal; Hyaluronic Acid; Antifungal Agents; Candida albicans; Nanoparticles
PubMed: 37379779
DOI: 10.1016/j.ejps.2023.106508