Nanoemulsion gel-based topical delivery of an antifungal drug:in vitroactivity andin vivoevaluation

Abstract

Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi, India AbstractObjective: In this study, attempt has been focused to prepare a nanoemulsion (NE) gel for topical delivery of amphotericin B (AmB) for enhanced as well as sustained skin permeation, in vitro antifungal activity and in vivo toxicity assessment. Materials and methods: A series of NE were prepared using sefsol-218 oil, Tween 80 and Transcutol-P by slow spontaneous titration method. Carbopol gel (0.5% w/w) was prepared containing 0.1% w/w AmB. Furthermore, NE gel (AmB-NE gel) was characterized for size, charge, pH, rheological behavior, drug release profile, skin permeability, hemolytic studies and ex vivo rat skin interaction with rat skin using differential scanning calorimeter. The drug permeability and skin irritation ability were examined with confocal laser scanning microscopy and Draize test, respectively. The in vitro antifungal activity was investigated against three fungal strains using the well agar diffusion method. Histopathological assessment was performed in rats to investigate their toxicological potential.Results and discussion: The AmB-NE gel (18.09 ± 0.6 mg/cm 2 /h) and NE (15.74 ± 0.4 mg/cm 2 /h) demonstrated the highest skin percutaneous permeation flux rate as compared to drug solution (4.59 ± 0.01 mg/cm 2 /h) suggesting better alternative to painful and nephrotoxic intravenous administration. Hemolytic and histopathological results revealed safe delivery of the drug. Based on combined results, NE and AmB-NE gel could be considered as an efficient, stable and safe carrier for enhanced and sustained topical delivery for AmB in local skin fungal infection. Conclusion: Topical delivery of AmB is suitable delivery system in NE gel carrier for skin fungal infection.

Optimized permeation enhancer for topical delivery of 5-fluorouracil-loaded elastic liposome using Design Expert: part II

“…Thus, the results suggested non-irritant and skin compatibility of gels containing permeation enhancer. Similar findings were reported in our preceding report using carbopol gel loaded with nanoemulsion of amphotericin B (Hussain et al, 2014b).…”

“…The pH was measured using digital electronic pH meter (Hanna Instrument HI 9321, Ann Arbor, MI). The preceding optimized EL3-S80 containing 5-FU was selected to incorporate into the freshly prepared carbopol-980 gel (1% w/v) as per method reported earlier (Hussain et al, 2014b). The final strength of 5-FU in 0.5% w/v gel was maintained at 5% w/w.…”

“…For suspension, 1 ml sample (EL suspension) was dispersed in 100 ml distilled water to get uniformly dispersed EL vesicles. Similarly, 1 g of gel containing EL was completely dispersed in 100 ml of distilled water to get homogeneous colloidal dispersion of EL for particle size and zeta potential measurement as reported earlier (Khurana et al, 2013;Hussain et al, 2014b). The particle size and surface (zeta potential) analysis of the prepared EL suspension and gel formulations were carried out using the photon correlation spectroscopy with a Malvern Nanosizer ZS (Malvern Instruments, Worcestershire, UK).…”

Formulation and optimization of nanoemulsion using antifungal lipid and surfactant for accentuated topical delivery of Amphotericin B

“…Antifungal assessment of various lipids and surfactants was determined using the agar well diffusion method with slight modification (Kadimi et al, 2007;Hussain et al, 2014b). The C. albicans (MTCC 4748) and A. niger (MTCC 282) were employed to culture into the Sabouraud Dextrose (SD) broth media at pH 6.8 for antifungal activities in term of the ZOI.…”

“…Now, vials were removed and centrifuged at 3000 rpm for 15 min to separate the supernatant for filtration using the membrane filter (0.45 mm). Finally, the content of AmB was estimated quantitatively using the UV-Vis Spectrophotometer (Shimadzu, U-1800 Spectrophotometer, Tokyo, Japan) at 382 nm by diluting with methanol (Hussain et al, 2014b).…”