Corneal targeted fenticonazole nitrate-loaded novasomes for the management of ocular candidiasis: Preparation, in vitro characterization, ex vivo and in vivo assessments

Abstract

The purpose of this manuscript was to develop and optimize Fenticonazole Nitrate (FTN)-loaded novasomes aiming to enhance drug corneal penetration and to improve its antifungal activity. Ethanol injection was used to formulate FTN-loaded novasomes adopting a central composite design. The researched factors were: stearic acid concentration (g%) (A), span 80: drug ratio (B) and cholesterol amount (mg) (C), and their effects on percent entrapment efficiency (EE%), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), and in vitro drug release after 8 hours (Q8h) were studied. Numerical optimization by Design-Expert® software was employed to select the optimum formula in respect to highest EE%, ZP (as absolute value), and Q8h >80% and lowest PS and PDI. Additional evaluation of the optimum formula was accomplished by short term stability study, effect of gamma sterilization, determination of Minimal Inhibitory Concentration and ex vivo corneal permeation study. The in vivo evaluation of the optimum formula was done to ensure its safety via in vivo ocular irritancy and in vivo corneal tolerance studies. Also, the efficacy was confirmed through in vivo corneal uptake study and susceptibility test. The optimum formula with the highest desirability value (0.738) showed EE% (94.31%), PS (197.05 nm), ZP (-66.95 mV) and Q8h (85.33%). It revealed to be safe, with augmented corneal permeation (527.98 µg/cm 2 ) that leads to higher antifungal activity. The above results confirmed the validity of novasomes to improve the corneal permeation and antifungal activity of Fenticonazole Nitrate.

Pronounced capping effect of olaminosomes as nanostructured platforms in ocular candidiasis management

“…Mobile phase of methanol-water (85:15, v/v run at consisted of) was filtered, degassed. The flow rate was 1.2 mL/min with an injection volume of 20 μL (Ahmed et al., 2022 ). The quantity of FTN penetrated per unit area (µg/cm 2 ) was graphed against time (h).…”

A comprehensive review on recent nanosystems for enhancing antifungal activity of fenticonazole nitrate from different routes of administration

“…They could be classified in this review according to the targeted site of action into ocular, topical or vaginal. Ocular nanosystems include olaminosomes (O-OLN), novasomes (O-NV) and terpesomes (O-TP) (Albash et al., 2021 ; Ahmed et al., 2022 a,b). Topical nanosystems resemble trans-novasomes (T-T-NV) and cerosomes (T-CE) (Albash et al., 2021 ; 2022 ).…”

“…In our study, various statistical designs were employed such as central composite, Box-Behnken, full factorial and D-optimal designs. Ocular novasomes (O-NV) and olaminosomes (O-OLN) were constructed using central composite design which was represented by twenty trials and Alpha of 1.68179 (Ahmed et al., 2022 a,b). However, ocular terpesomes (O-TP) and topical cerosomes (T-CE) were formulated utilizing full factorial designs (Albash et al., 2021 a,b).…”

“…In ethanol injection method, FTN and other components were dissolved in ethanol at 60 °C. Then the resulted solution was injected dropwise into larger-volume of phosphate-buffered saline (PBS, pH 7.4) (Ahmed et al., 2022 a,b) or distilled water and magnetically stirred at the same temperature till disappearance of alcohol (Albash et al., 2022 ). The final product was sonicated to reduce the PS then stored at 4 °C (Al-Mahallawi et al., 2014 ).…”

“…The aqueous solubility of FTN represents its main drawback as it is less than 0.10 mg/mL. Poor aqueous solubility could significantly affect the drug activity or even results in microbial resistance, thereby novel nanosystems had been developed (Ahmed et al., 2022 ).…”