Antifungal Cationic Nanoemulsion Ferrying Miconazole Nitrate with Synergism to Control Fungal Infections:In Vitro,Ex Vivo, andIn VivoEvaluations

Abstract

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/cm 2 /h), high drug deposition (932.7 ± 41.6 μg/cm 2 ), 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 characterization of amphotericin B nanoemulsion-loaded mucoadhesive gel for treatment of vulvovaginal candidiasis

“…found that incorporating an amphoteric acyclovir into NE increased its solubility and caused a two-fold increase in its skin permeation when compared to the marketed gel [ 21 ]. Similar findings were made for a miconazole nitrate nanoemulsion, where the researchers discovered that encapsulating the miconazole nitrate within the oil globules of Peceol (oil phase) resulted in decreased haemolysis and toxicity, as well as improved permeability and solubility [ 22 ]. Drawing spur from the aforementioned research articles, authors of the current investigation have developed an oil-in-water (o/w) nanoemulsion loaded with AmB (AmB-NE) to tackle difficulties associated with conventional AmB therapy.…”

Hansen Solubility Parameters and QbD-Oriented HPLC Method Development and Validation for Dermatokinetic Study of a Miconazole-Loaded Cationic Nanoemulsion in Rat Model

“…As mentioned before, we reported in vitro and in vivo behaviors of the MCZ-loaded nanoemulsion and cationic nanoemulsion after topical application onto rat skin and their permeation profile. It was required to develop and validate a HPLC method for the rat skin tissue to quantify the drug content and permeated drug concentration for the same formulations at high sensitivity, simplicity, and reproducibility. , These reported formulations were designated as MCNE11 (miconazole cationic nanoemulsion), MNE11 (miconazole nanoemulsion), MCZ-MKT (marketed gel), and MCZ-Sol (miconazole drug suspension). Nanoemulsions were composed of biocompatible lipid (peceol) and labrasol as a hydrophilic surfactant (hydrophilic lipophilic balance, HLB = 13.2).…”

“…Oleylamine served as a positive charge inducer and was expected to internalize with the negatively charged cellular surface of skin for maximized adhesion and subsequent drug permeation and drug penetration via electrostatic interactions. Other variables were kept constant to investigate the impact of positively charged nanoscale globular mediated enhanced permeation as discussed in the previous report . In the present study, it was required to develop an efficient, simple, and reproducible economic bioanalytical method for the quantitative estimation of MCZ from rat skin samples treated with MCNE11 and MNE11.…”

“…The developed and validated method was successfully implemented to study PK parameters (in vivo dermatokinetics) of MCZ in rat plasma after the dermal application of the aforementioned formulations. Previously, we explored product development, product optimization, and in vitro–ex vivo studies using suitable models . Furthermore, a validated method with high sensitivity and reproducibility was established to confirm localized and systemic (in vivo) performance of the developed formulations (MCNE11, MNE11, MCZ-MKT, and MCZ-Sol) for their therapeutic efficacy.…”

“…Each group contained three rats. A dorsal area (3 cm 2 ) on each rat was properly shaved to apply (1 mg/0.5 mL) the formulations (MCZCNE11, MCZNE11, MCZ-MKT, and MCZ-DS gel). , The blood (0.5 mL) sample was withdrawn from the retro-orbital plexus at different time points (0.0, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 h). Each sample was ultracentrifuged to a clear supernatant.…”