Miconazole Research Articles

Synergistic Activity of Ketoconazole and Miconazole with Prochloraz in Inducing Oxidative Stress, GSH Depletion, Mitochondrial Dysfunction, and Apoptosis in Mouse Sertoli TM4 Cells.

Triazole and imidazole fungicides represent an emerging class of pollutants with endocrine-disrupting properties. Concerning mammalian reproduction, a possible causative role of antifungal compounds in inducing toxicity has been reported, although currently, there is little evidence about potential cooperative toxic effects. Toxicant-induced oxidative stress (OS) may be an important mechanism potentially involved in male reproductive dysfunction. Thus, to clarify the molecular mechanism underlying the effects of azoles on male reproduction, the individual and combined potential of fluconazole (FCZ), prochloraz (PCZ), miconazole (MCZ), and ketoconazole (KCZ) in triggering in vitro toxicity, redox status alterations, and OS in mouse TM4 Sertoli cells (SCs) was investigated. In the present study, we demonstrate that KCZ and MCZ, alone or in synergistic combination with PCZ, strongly impair SC functions, and this event is, at least in part, ascribed to OS. In particular, azoles-induced cytotoxicity is associated with growth inhibitory effects, G0/G1 cell cycle arrest, mitochondrial dysfunction, reactive oxygen species (ROS) generation, imbalance of the superoxide dismutase (SOD) specific activity, glutathione (GSH) depletion, and apoptosis. N-acetylcysteine (NAC) inhibits ROS accumulation and rescues SCs from azole-induced apoptosis. PCZ alone exhibits only cytostatic and pro-oxidant properties, while FCZ, either individually or in combination, shows no cytotoxic effects up to 320 µM.

Review of Treatments for Oropharyngeal Fungal Infections in HIV/AIDS Patients

HIV and AIDS patients are susceptible to opportunistic infections. Oral candidiasis or thrush is the primary manifestation of fungal infection in these patients. The primary objective of this literature review was to summarize established and novel treatment options for oropharyngeal fungal infections in HIV/AIDS patients. Azoles and polyenes are the two primary antifungal drug classes employed for the treatment of oral candidiasis. A literature review was conducted on Medline and Google Scholar in October of 2021 using the keywords “Oral”, “Fungal”, “HIV”, and “Treatment”. Included studies were clinical trials, meta-analyses, and randomized controlled trials. Nineteen studies regarding azoles, polyenes, and novel treatments for oropharyngeal fungal infections in HIV/AIDS patients were examined in this review. The primary concern demonstrated from these studies is increased reports of resistance to antifungals, especially development of fluconazole resistance. Additionally, studies demonstrated that fluconazole had different relapse durations comparative to other medications, and that posaconazole could possibly act as an alternate form of treatment. Nystatin was indicated as a first-line therapy for thrush in multiple studies but could be upstaged by miconazole nitrate in resource-poor settings. Amphotericin B was an effective treatment option and was shown to be resilient in terms of fungal resistance, however potent adverse side effects were reported. Alternative treatments, such as immunoglobulin antibodies and lemon grass, revealed promising antifungal effects for immunocompromised individuals. Taken together, this review provides a thorough summary of treatment options of oropharyngeal fungal infections in HIV/AIDS patients.

Antifungal Cationic Nanoemulsion Ferrying Miconazole Nitrate with Synergism to Control Fungal Infections: In Vitro, Ex Vivo, and In Vivo Evaluations.

This study aimed to deliver a cationic nanoemulsion carrying miconazole nitrate (MCN) to control fungal infections using excipients for synergism. Peceol (oil) and labrasol (surfactant) were selected based on maximum solubility and zone of inhibition values against Candida albicans and Aspergillus niger. Optimized MCNE11 was evaluated [size, zeta potential, % entrapment efficiency (%EE), % transmittance, viscosity, refractive index, extrudability, polydispersity (PDI), morphology, and pH]. An in vitro drug release study was conducted for comparison between DS (drug suspension) and MNE11. In vitro hemolysis was studied at two different concentrations (0.625 and 2.5 μg/mL). Permeation profiles were generated using rat skin. A Draize test was conducted using rabbit to negate irritability issues. Finally, a stability test of MCNE11 was conducted for 12 months. The results showed that MCNE11 (cationic) was the most optimized in term of size, %EE, and PDI. The drug release from MCNE11 was higher compared to DS but comparable to MNE11 (anionic), suggesting no impact of the imposed cationic charge on the release behavior. Moreover, permeation parameters of MCNE11 were significantly (p < 0.05) greater than MNE11, which may be attributed to the combined impact of size (low), surfactant (for reversible changes), and electrostatic interaction (nanoglobules–skin surface). Thus, stable MCN11 possessing high %EE (89.8%), low size (145 nm), maximum flux (5.7 ± 0.1 μg/cm2/h), high drug deposition (932.7 ± 41.6 μg/cm2), optimal viscosity (44.17 ± 0.8 cP), low PDI (0.21), optimal zeta potential (+28.1 mV), and low hemolysis can be promising alternatives to conventional cream to control resistant and recurring types of fungal infections.

Development and Evaluation of a Film Forming System Containing Myricetin and Miconazole Nitrate for Preventing Candida albicans Catheter-Related Infection.

Background: Candida albicans catheter-related infection (CRI) is a great challenge in clinic now, mainly due to the difficulty in eradicating the biofilms. Purpose: In this study, the mechanism of the antibiofilm effect of myricetin (MY) on C. albicans was illustrated. A film forming system (FFS) containing MY and miconazole nitrate (MN) was developed, optimized, and evaluated. The anti-infection effect of MY+MN@FFS against C. albicans CRI was investigated in vivo. Study Design and Methods: To clarify the mechanism of the action of MY, the influence of MY on each key process of the formation of C. albicans biofilms was evaluated. To deliver MY and MN into the skin and form a drug reservoir on the surface of the skin, the FFS was used as a carrier and MY+MN@FFS was developed, optimized, and evaluated. After preliminary confirmation of drug safety, a percutaneously inserted C. albicans CRI mouse model was established to investigate the in vivo anti-infection effect of MY+MN@FFS by fluorescence microscopy and scanning electron microscopy on the outer surface of the catheters, hematoxylin/eosin staining, and periodic acid-Schiff staining of the mice skin tissues. Results: MY was found to inhibit the morphological transition of C. albicans and the secretion of exopolysaccharides, resulting in a reduction in biofilms. MY+MN@FFS exhibited excellent properties and no irritation to mice skin. In an in vivo anti-infection study, MY+MN@FFS exhibited an excellent preventive effect against percutaneously inserted C. albicans CRI. Conclusion: MY+MN@FFS might be a potential approach for effectively preventing percutaneously inserted C. albicans CRI in clinic.

Multicenter prospective observational study of fungal keratitis in Japan: analyses of in vitro susceptibility tests for combinations of drugs.

To determine the effects of a combination of two antifungal drugs against causative fungi of fungal keratitis in Japan. Multicenter prospective observational study. Eighteen isolates of yeast-like fungi and 22 isolates of filamentous fungi collected by the Multicenter Prospective Observational Study of Fungal Keratitis in Japan were studied. Specially manufactured minimum inhibitory concentration (MIC) measurement plates were used to test the effectiveness of 10 combinations of two antifungal drugs against the isolates. The combinations were pimaricin (PMR) + voriconazole (VRCZ), PMR + fluconazole (FLCZ), PMR + miconazole (MCZ), PMR + micafungin (MCFG), VRCZ + FLCZ, VRCZ + MCZ, VRCZ + MCFG, VRCZ + amphotericin-B (AMPH-B), MCZ + FLCZ, and MCZ + MCFG. The checkerboard microdilution method was used, and the fractional inhibitory concentration (FIC) index was calculated based on the guidelines of The Clinical & Laboratory Standards Institute (CLSI). In yeast-like fungi,additive effects were observed between PMR and MCFG in 77.8% of the isolates, and they were also observed between the azoles. Synergistic effects were observed on 11.1% of the isolates for MCZ and FLCZ. On the other hand, antagonistic effects were present between PMR and azoles with 88.9% between PMR and VRCZ, 72.2% between PMR and FLCZ, and 94.4% between PMR and MCZ. In filamentous fungi,additive effects were observed between PMR and MCFG in 40.9% of the isolates, and between VRCZ and MCZ in 40.9% of the isolates. Antagonistic effects were observed for PMR and the azoles. The combination of drugs prescribed for fungal keratitis incurs a possibility of synergistic, additive, indifferent, or antagonistic effects, depending on drug combinations and fungal strains.

High-Resolution Ultrasound Spectroscopy for the Determination of Phospholipid Transitions in Liposomal Dispersions.

High-resolution ultrasound spectroscopy (HR-US) is a spectroscopic technique using ultrasound waves at high frequencies to investigate the structural properties of dispersed materials. This technique is able to monitor the variation of ultrasound parameters (sound speed and attenuation) due to the interaction of ultrasound waves with samples as a function of temperature and concentration. Despite being employed for the characterization of several colloidal systems, there is a lack in the literature regarding the comparison between the potential of HR-US for the determination of phospholipid thermal transitions and that of other common techniques both for loaded or unloaded liposomes. Thermal transitions of liposomes composed of pure phospholipids (dimyristoylphosphatidylcholine, DMPC; dipalmitoylphosphatidylcholine, DPPC and distearoylphosphatidylcholine, DSPC), cholesterol and their mixtures were investigated by HR-US in comparison to the most commonly employed microcalorimetry (mDSC) and dynamic light scattering (DLS). Moreover, tramadol hydrochloride, caffeine or miconazole nitrate as model drugs were loaded in DPPC liposomes to study the effect of their incorporation on thermal properties of a phospholipid bilayer. HR-US provided the determination of phospholipid sol-gel transition temperatures from both attenuation and sound speed that are comparable to those calculated by mDSC and DLS techniques for all analysed liposomal dispersions, both loaded and unloaded. Therefore, HR-US is proposed here as an alternative technique to determine the transition temperature of phospholipid membrane in liposomes.

Stability mechanisms for microwave-produced solid lipid nanoparticles

Tween® 20 stabilised stearic acid solid lipid nanoparticles (SLNs) were prepared using a one-pot microwave-assisted microemulsion technique. Two model water-insoluble drugs, the carboxylic acid-based indomethacin, and the imidazole-based miconazole nitrate, were then used to load the SLNs, and their subsequent physical properties (particle size and zeta potential) were measured and used to predict dispersion stability.Drug-free SLNs had a particle size of 239 nm and a zeta potential of − 29 mV. Indomethacin-loaded SLNs had a particle size of 266 nm and zeta potential of − 30 mV. Miconazole-loaded SLNs had a particle size of 266 nm and zeta potential of + 15 mV. These values were found to be relatively stable (under mildly acidic conditions) and recommend the suitability of the SLNs as a drug carrier.In all cases, the particle size and zeta potential were shown to be pH-dependent. For particle size, a minimum value was obtained at approximately pH 5, which corresponds to the pKa of the lipid used (stearic acid) indicating stearic acid adsorption onto the surface is likely to be at least partly responsible for dispersion stability. We conclude that dispersion stability arises from a combination of electrostatic stability (from adsorbed stearic acid) and limited steric stability from non-ionic (Tween® 20) surface-associated micelles.Dispersions were found to be unstable under alkaline conditions despite the increasingly negative zeta potential of all dispersions. This was observed as an increasingly larger particle size at pH > 7 combined with the observation that particle sizes at pH > 7 were also unstable and continued to increase with time. Visual observations showed dispersions physically broke within a few days at pH values > 7.The encapsulation efficiency (EE) and loading capacity (LC) of drug-loaded SLNs were shown to be close to their theoretical maximum (100%) at low pH, but decreased to < 20%, in the case of indomethacin-loaded SLNs, at a pH >> 7. Interestingly, the EE and LC of miconazole-loaded SLNs when first formed were relatively unaffected by pH. pH control, therefore, is very important to particle stability, and the pH should be kept neutral to mildly acidic.

Preparation, physicochemical characterization, and In vivo evaluation of miconazole nitrate nanosponges for the treatment of systemic mycoses

Miconazole is a Biopharmaceutics Classification System (BCS) class II drug, thus limiting its oral bioavailability. Nanosponges can improve the oral bioavailability of poorly soluble drugs and sustain their release. The work was aimed at formulating miconazole nanosponges to enhance its solubility and consequently, oral bioavailability. Batches of nanosponges incorporating different concentrations (1, 2 and 3 %) of miconazole nitrate were formed using ethyl cellulose (EC), polyvinyl alcohol (PVA), ethanol and Kolliphor® 188. They were characterized using percentage yield, encapsulation efficiency, Differential Scanning Calorimetry (DSC), Xray Diffraction (XRD), particle sizes, polydispersity index (PDI) and Scanning Electron Microscopy (SEM). In vitro antifungal evaluation against Candida albicans was assessed while in vitro release using simulated gastric fluid was done. Furthermore, in vivo release studies in rats were carried out using the bioassay method. The percentage yield of the nanosponges were between 50 to 60 %. Encapsulation efficiencies ranged between 77 and 98 %. Particle sizes ranged between 266.5 and 781.1 nm. Particles were porous and spongy in appearance. Antifungal evaluation of the nanosponges against Candida albicans revealed activity like that of the pure drug. In vitro release studies showed a sustained release pattern for the nanosponges up till 12 hours whereas the unformulated drug peaked at 2 h. In vivo evaluation showed a concentration dependent increase in blood concentration of the drug with NS4 having the highest release. Nanosponges containing miconazole nitrate were successfully formulated and evaluated and are a promising oral delivery system for miconazole nitrate.

Miconazole Nitrate loaded Soluplus®-Pluronic® nano-micelles as promising Drug Delivery Systems for Ocular Fungal Infections: In vitro and In vivo Considerations

Miconazole nitrate (MN) is a broad-spectrum antifungal agent which suffers poor solubility and impermeability to the ocular tissue which limits its use in the treatment of ocular infections especially fungal keratitis, which is considered one of the most prevailing ocular infections. The current study aims to utilize polymeric mixed nano-micelles for the ocular delivery of MN using 33 full factorial design by varying the ratios of Pluronic® P123, Pluronic® F127, and Tetronic® T701 while the monitored responses were particle size, cloud point (CP), encapsulation efficiency (%EE) and %released at 6 hours (%Q6) at pH 7.4. The optimized formula was incorporated with Soluplus® (SP) to further enhance the (%EE) and the resultant formula was assessed in vitro as well as in vivo against C. albicans in treatment of induced ocular candidiasis using rabbits as a model animal. Results revealed that the optimized formula which comprised F127 and P123 in a ratio of (2:1) when incorporated with SP (SP-MPM) resulted in an increase in %EE from 35.12±3.18 to 99.19±7.03 with a particle size of 44.39±2.68nm with a sustained release profile and stability for 3 months at 4±2°C. In vivo results demonstrated the enhanced ability of SP-MPM for treatment of ocular candidiasis with enhanced % inhibition and susceptibility to C. albicans compared to 0.2% MN suspension confirmed with histopathological examination of rabbit’s eyes after 7 days of treatment with the absence of any degenerative effect to the ocular tissue. Thus, it can be concluded that SP-pluronic mixed nano-micelles offer a successful and stable ocular delivery platform for antifungal drug MN ensuring both its safety and efficacy.

Miconazole Nitrate–Loaded Solid Lipid Nanoparticle-Based Hydrogel Ameliorate Candida albicans Induced Mycoses in Experimental Animals

Miconazole Nitrate–Loaded Solid Lipid Nanoparticle-Based Hydrogel Ameliorate Candida albicans Induced Mycoses in Experimental Animals

Factorial Design Executed Development of Miconazole Nitrate Microemulsion Based Bioadhesive Gel and Its Evaluation

Miconazole nitrate (MN) is a poorly aqueous soluble antifungal drug. The microemulsion (ME) based bioadhesive antifungal gel of MN was designed to improve the antifungal activity by increasing the bioadhesion potential. Based on the solubility results, components of ME were selected viz. rice bran oil: tween 80: propylene glycol and proceeded with pseudo-ternary phase diagram studies. 23 factorial design was employed for the formulation of MEs employing water titration technique. The MEs was examined for further studies and was optimized using DESIGN EXPERT 12 software considering the responses like globule size, zeta potential and in vitro drug release. Tamarind seed polysaccharide (TSP) and carbopol 934 were used as gel bases for the formulation of microemulsion-based bioadhesive gels. The gels were examined for drug content, pH, spreadability, viscosity, bioadhesive strength, ex vivo drug permeation and in vivo skin irritation potential. The antifungal activity against Candida albicans and Cryptococcus neoformans of four formulations (MN-ME, MN- ME based TSP gel, MN- ME based carbopol gel and marketed miconazole gel (2% Miconazole gel) was evaluated using modified agar diffusion method. The results revealed that microemulsion based bioadhesive gel (MBG) of TSP and CP exhibited drug content of about 87.29% and 83.34% and ex vivo skin permeation of 84.21% and 73.94% at the end of 10 h. MBG of TSP showed better antifungal activity and no skin irritation potential in comparison to the carbopol gel. Therefore, MBG of TSP has the ability to enhance the contact time owing to greater bioadhesion thereby providing a better therapeutic activity. Keywords: Miconazole nitrate, Tamarind Gum, Topical delivery, Microemulsion based bioadhesive gel, fungal infection.

Denture Adhesive Containing Microparticles for Delivery of Miconazole: In Vivo Toxicity

The choice treatment for denture stomatitis are topical antifungals such as miconazole nitrate (MN). Targeting denture wearers, an experimental denture adhesive (EA) was developed containing polymeric microparticles (MPs) for the delivery of MN. Objectives: To investigate the systemic toxicity in rats of the EA added with MN MPs. Methods: Thirty-five Wistar rats received intraperitoneal injection of the materials: artificial saliva (AS) as solvent, Corega Cream® (CCDA), pure EA or EA added with MN MPs (sigla), and pure MN or MNMP. Animal behavior impairment (level 0-4) and weight (g) analyses were carried out at 0, 24, 48 and 72 h. Blood was collected to detect C-reactive protein. The intraperitoneal washing was analyzed through red blood cell and leukocyte counts and turbidity degree. Descriptive statistical analysis was performed for behavior and turbidity. Normality of red blood cells (thousand/L) and leukocytes (million/L) counts was verified (Shapiro-Wilk, p&lt;0.0001). Statistical analysis was performed using Kruskall-Wallis and Mann-Whitney U tests with Bonferroni adjustment. Results: No significant difference between weights of groups was found for time (p=0,551). No behavior alterations level 2, 3 or 4 were observed. The C-Reactive protein was negative for all groups. The leukocyte and red blood cell counts showed significant difference between the groups AS and EA+MNMP (p=0.016 and p=0.009, respectively). No significant difference was found between EA+MNM and the CCA (p=0.917) group in the leukocyte count. Significance: The denture adhesive with antifungal presented similar results to those of the commercially available adhesive, and pure saliva was sufficient to cause peritoneum systemic toxicity.

Solidified Reverse Micellar Solution- (SRMS-) Based Microparticles for Enhanced Oral Bioavailability and Systemic Antifungal Efficacy of Miconazole Nitrate in Immunocompromised Mice.

Purpose To assess the improvement in oral bioavailability and efficacy in systemic candidiasis treatment of miconazole nitrate (MN) formulations in murine models of candidiasis. Methods Selected formulations containing 5% of Softisan + Phospholipon 90H lipid matrix with 3% of MN (A1), 5% of stearic acid + Phospholipon 90H lipid matrix with 3% of MN (B1), and 5% Softisan + stearic acid + Phospholipon 90H with 3% of MN (C1) from the in vitro investigation were used for the study. Their acute toxicity was assessed using Lorke's method (with slight modification) while bioavailability was determined using the bioassay method. The optimized batch (A1) was tested in murine systemic candidiasis induced in cyclophosphamide-immunosuppressed mice. The mice were treated with a single oral dose (100 mg/kg) of the formulations for five days. Serum fungal counts (cfu/mL) were determined on days 1, 3, and 5 of the treatment period. Haematological assessments were done. Results The lipid formulations were safer than MN powder with LD50 values of 3162.8 and 1118.3 mg/kg. Bioavailability determination revealed a higher area under the curve (AUC) value for formulations A1 (6.11 μg/hr/mL) and B1 (4.91 μg/hr/mL) while formulation C1 (1.80 μg/hr/mL) had a lower AUC than MN (4.46 μg/hr/mL). Fungi were completely cleared from the blood of animals treated with the optimized formulation by day 3 as opposed to the controls (MN and Tween® 20) which still had fungi on day 5. No significant increase (p > 0.05) in haematological parameters was observed in mice treated with A1. Conclusion Formulation A1 successfully cleared Candida albicans from the blood within a shorter period than miconazole powder. This research has shown the potential of orally administered MN-loaded SRMS-based microparticles in combating systemic candidaemia.

Novel Bos indicus Fat-Based Nanoparticulate Lipospheres of Miconazole Nitrate as Enhanced Mucoadhesive Therapy for Oral Candidiasis

Nanoparticulate lipospheres of miconazole nitrate were formulated and incorporated into mucoadhesive gels for enhanced treatment of oral candidiasis. Extracted cow fat and Phospholipon® 90H (7:3) were used to prepare a lipid matrix by fusion. Nanoparticulate lipospheres with drug concentrations (0, 0.125, 0.25, 0.5 % w/w) were prepared using the lipid matrix (5.0 % w/w), polysorbate 80 (2.0 % w/w), sorbitol (4.0 % w/w) and distilled water by melt homogenization. The lipospheres characterized encapsulation efficiency (EE), drug loading capacity (DL), particle size, polydispersity index, morphology, and compatibility. Lipid-based gels were prepared using Polycarbophil® (1.0 % w/w), the nanoparticles and other excipients, by dispersion, then characterized regarding drug content, compatibility, rheology, ex-vivo mucoadhesive, in-vitro drug release, and anti-candidal activity. The EE, DL, and mucoadhesive strengths of the formulated gels were influenced by drug loads. The particles were smooth, nanometric, and spherical, with polydispersity indices in the range of 0.247 ‒ 0.293. The gels were pseudoplastic. The gels ' extensive drug release profiles and anti-candidal activity were significantly superior to commercial Daktarin®. FT-IR confirmed the compatibility of the drug with excipients used in the formulations. The prospects of this study necessitate further optimization.

Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: in vitro and ex vivo evaluation

Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi’s diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm2) than LNCs (12.7 ± 1.52 µg/cm2). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.

Development, optimization, and evaluation of a nanostructured lipid carrier of sesame oil loaded with miconazole for the treatment of oral candidiasis

Candida albicans is the fungus responsible for oral candidiasis, a prevalent disease. The development of antifungal-based delivery systems has always been a major challenge for researchers. This study was designed to develop a nanostructured lipid carrier (NLC) of sesame oil (SO) loaded with miconazole (MZ) that could overcome the solubility problems of MZ and enhance its antifungal activity against oral candidiasis. In the formulation of this study, SO was used as a component of a liquid lipid that showed an improved antifungal effect of MZ. An optimized MZ-loaded NLC of SO (MZ-SO NLC) was used, based on a central composite design-based experimental design; the particle size, dissolution efficiency, and inhibition zone against oral candidiasis were chosen as dependent variables. A software analysis provided an optimized MZ-SO NLC with a particle size of 92 nm, dissolution efficiency of 88%, and inhibition zone of 29 mm. Concurrently, the ex vivo permeation rate of the sheep buccal mucosa was shown to be significantly (p < .05) higher for MZ-SO NLC (1472 µg/cm2) as compared with a marketed MZ formulation (1215 µg/cm2) and an aqueous MZ suspension (470 µg/cm2). Additionally, an in vivo efficacy study in terms of the ulcer index against C. albicans found a superior result for the optimized MZ-SO NLC (0.5 ± 0.50) in a treated group of animals. Hence, it can be concluded that MZ, through an optimized NLC of SO, can treat candidiasis effectively by inhibiting the growth of C. albicans.

Formulasi Sediaan Salep Ekstrak Minyak Atsiri Daun Jeruk Purut (Citrus Hystrix DC.) terhadap Jamur Candida Albicans

&lt;p&gt;&lt;em&gt;T&lt;/em&gt;&lt;em&gt;he purpose of this&lt;/em&gt;&lt;em&gt; study &lt;/em&gt;&lt;em&gt;was&lt;/em&gt;&lt;em&gt; to formulate essential oils in ointment preparations with different bases and to determine the physical properties and antifungal activity against Candida albicans.&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;The essential oil of kaffir lime leaves was obtained by distillation using the water distillation method and the raw material of fresh kaffir lime leaves was 1.5 k&lt;/em&gt;&lt;em&gt;ilograms&lt;/em&gt;&lt;em&gt; which was then identified with Sudan III reagent and formulated in ointment preparations.&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;The ointment is made with FI, FII, and FIII base formulations with an active substance concentration of 7%. The FIII ointment base had the best evaluation results and was continued for antifungal testing against Candida albicans.&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;From the research results obtained % yield of essential oil of kaffir lime leaves is 1.533%. The results of the phytochemical identification test showed positive results with the formation of an even red color in the solution.&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;The results of the evaluation of the ointment preparations showed that FIII had the best evaluation results and continued antifungal testing with a positive control of 2% miconazole nitrate cream.&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;The average diameter obtained is 8.43 mm and is included in the medium category.&lt;/em&gt;&lt;em&gt; &lt;/em&gt;&lt;em&gt;The results of the Shapiro Wilk normality test showed that the research data was normally distributed and homogeneous, then the One-Way ANOVA test was carried out and a significance value of P&amp;lt;0.05 was obtained, and the LSD test showed a significant difference seen from the significance value obtained P&amp;lt;0.05.&lt;/em&gt;&lt;em&gt;&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;em&gt; &lt;/em&gt;&lt;/p&gt;

STATISTICAL OPTIMIZATION AND EVALUATION OF ETHOSOMAL MICONAZOLE NITRATE SUSPENSION

Objective: The objectives of the present study were to optimize and evaluate the ethosomal suspension of miconazole nitrate for the treatment of local and systemic fungal infections. Methods: Miconazole topical formulation is prepared for better patient compliance and to reduce the dose of a drug. Miconazole nitrate ethosomes were prepared by the cold method using factorial designing with Ethanol(X1), IPA(Isopropyl alcohol)(X2), and Lecithin(X3) as Independent variables and % EE(Entrapment efficiency)(Y1) and % DR(drug release at 8th h)(Y2) was selected as responses. Results: The results obtained in the design showed that there was no significant interaction among factors. The lecithin concentration had a positive response on % EE, while ethanol concentration and IPA had a positive effect. For % DR, Ethanol, and IPA showed a positive effect and Lecithin had a negative response. The formulation EM22 (3 ml X1,3 ml X2 and 300 mg of X3) characterized by high % EE(77.3 %) and optimum % DR(94.2%) and formulation EM6 (2 ml X1,2 ml X2 and 100 mg of X3) characterized by high % DR(97.32 %) and optimum % EE (74.8 %). EM22 was incorporated in the gel as it is showing more entrapment efficiency and compared with the marketed product for drug release. Conclusion: From the result, it was concluded that formulated ethosomal suspension and optimized gel have more drug release than marketed formulation so that formulated suspension can be used for the preparation of antifungal gels, creams, ointments for sustained release.

Investigating the Contribution of Drug-Metabolizing Enzymes in Drug-Drug Interactions of Dapivirine and Miconazole.

Dapivirine (DPV) is a potent NNRTI used to prevent the sexual transmission of HIV. In a phase 1 trial (IPM 028), the concomitant use of a DPV vaginal ring and an antifungal miconazole (MIC) vaginal capsule was found to increase the systemic exposure to DPV in women, suggesting a potential for drug-drug interactions. This study’s objective was to investigate the mechanism of DPV-MIC interactions using drug-metabolizing enzymes (DMEs; CYPs and UGTs) that are locally expressed in the female reproductive tract (FRT). In vitro studies were performed to evaluate the metabolism of DPV and its inhibition and induction potential with DMEs. In addition, the impact of MIC on DPV metabolism and the inhibitory potential of DPV with DMEs were studied. Our findings suggest that DPV is a substrate of CYP1A1 and CYP3A4 enzymes and that MIC significantly decreased the DPV metabolism by inhibiting these two enzymes. DPV demonstrated potent inhibition of CYP1A1 and moderate/weak inhibition of the six CYP and eight UGT enzymes evaluated. MIC showed potent/moderate inhibition of seven CYP enzymes and weak/no inhibition of eight UGT enzymes. The combination of DPV and MIC showed potent inhibition of seven CYP enzymes (1A1, 1A2, 1B1, 2B6, 2C8, 2C19, and 3A4) and four UGT enzymes (1A3, 1A6, 1A9, and 2B7). DPV was not an inducer of CYP1A2, CYP2B6, and CYP3A4 enzymes in primary human hepatocytes. Therefore, the increased systemic concentrations of DPV observed in IPM 028 were likely due to the reduced metabolism of DPV because of CYP1A1 and CYP3A4 enzymes inhibition by MIC in the FRT.

Comparative Evaluation of Effectiveness of Denture Adhesive after Incorporating Antifungal Agent – An In-vitro Study

Aims: The aim of current study is to evaluate adhesive force and qualitative mycological culture analysis of Denture adhesive (DA) after incorporating antifungal agent in various concentrations.&#x0D; Study Design: Experimental study.&#x0D; Place and Duration of Study: The current study was conducted at the Department of Prosthodontics, Mansarovar Dental College and Hospital, Bhopal (M. P.) from September 2017 to October 2018.&#x0D; Methodology: A total of 80 specimens were prepared with heat cured acrylic resin, out of which 40 were used for qualitative anti-microbiological test, and 40 were used for Adhesive force measurement test. Both test had four groups: Group A (Control group DA without MN); Group B (DA+MN 10%); Group C (DA+MN 20%); and Group D (DA+MN 30%).&#x0D; Results: The mean zone of inhibition was 8.85 ± 0.28 mm for 10% w/w Miconazole Nitrate (MN), 12.95±0.30 mm for 20% w/w MN, and 22.25 ± 0.38 mm for 30% w/w MN. There was a statistically highly significant (P&lt; .001) difference between the groups, with an F value of 1077.8.&#x0D; Conclusion: Within the limitation of the study qualitative anti-microbial property for favorable laboratory performance can be achieved only after the addition of 20% w/w Miconazole Nitrate to denture adhesive paste.