A comparative ex vivo permeation evaluation of a novel 5-Fluorocuracil nanoemulsion-gel by topically applied in the different excised rat, goat, and cow skin

Niyaz Ahmad; Rizwan Ahmad; Taysser Mohammed Buheazaha; Hussain Salman AlHomoud; Hassan Ali Al-Nasif; Md Sarafroz

doi:10.1016/j.sjbs.2020.02.014

A comparative ex vivo permeation evaluation of a novel 5-Fluorocuracil nanoemulsion-gel by topically applied in the different excised rat, goat, and cow skin

Saudi J Biol Sci. 2020 Apr;27(4):1024-1040. doi: 10.1016/j.sjbs.2020.02.014. Epub 2020 Mar 3.

Authors

Niyaz Ahmad^{1

2}, Rizwan Ahmad³, Taysser Mohammed Buheazaha¹, Hussain Salman AlHomoud¹, Hassan Ali Al-Nasif¹, Md Sarafroz²

Affiliations

¹ Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
² Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
³ Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Abstract

Aim of the study: 5-Fluorouracil (5-FU) can't be given orally because of very low bioavailability and produces serious adverse effects. Therefore, the main objective of this research is to develop, evaluate, and comparative effects by different nanoformulations of topical application on chemoprevention of skin cancer in different types of skin.

Material and methods: Castor oil (oil), Transcutol HP (surfactant), and Polyethylene glycol (PEG)-400 (co-surfactant) have taken on the basis of nonionic property and highest nanoemulsion (NE)-region. Aqueous micro titration method with ultra-sonication method (based on high energy) was used for the preparation of 5-FU-NE. Optimized-5-FU-NE was stable thermodynamically, and their characterizations was performed on the basis of globule size, zeta potential, refractive index, and viscosity. Optimized-NE has been converted into 5-FU-NE-Gel with the help of Carbopol® 934 and also performed their permeation studies in the different skins (cow, goat, and rat, ex vivo) using Logan transdermal diffusion cell (DHC-6T). Optimized-5-FU-NE and 5-FU-NE-Gel were evaluated cytotoxic studies (in vitro) on the melanoma cell lines.

Results: The permeation of 5-FU from 5-FU-NE-Gel nanoformulation for rat skin model was 1.56 times higher than the 5-FU-NE and 12.51 times higher than the 5-FU-S for the cow and goat skin model. The values of steady state flux and permeability coefficient for 5-FU-NE-Gel of rat skin were higher i.e. 12.0244 ± 1.12 µgcm^-2h^-1 and 1.2024 ± 0.073 × 10^-2 µg cm^-2h^-1, respectively. Optimized-5-FU-NE and 5-FU-NE-Gel nanoformulation were found to be physically stable. SK-MEL-5 cancer cells have showed the results based on cytotoxicity studies (in vitro) that 5-FU as Optimized-5-FU-NE-Gel is much more efficacious than 5-FU-NE followed by free 5-FU. Localization of 5-FU from 5-FU-NE-Gel was higher with higher permeation in rat skin.

Conclusion: 5-FU-NE-Gel is found to be for the better to treatment of cutaneous malignancies. It can be developed 5-FU-NE-Gel could be a promising vehicle for the skin cancer chemoprevention.

Keywords: 5-FU, 5-Fluorouracil; 5-FU-NE-Gel, 5-Fluorouracil Nanoemulsion Gel; 5-Fluorouracil; ANOVA, Analysis of variance; BCS, Biopharmaceutical Classification System; Cytotoxic activity; DDTC, Diethyldithiocarbamate; DSC, Differential Scanning Calorimetry; Different skin permeation, chemoprevention; Electrospray Ionization, ESI; Er, Enhancement Ratio; FT-IR, Fourier-transform infrared spectroscopy; Kp, Permeability Coefficient; Local accumulation efficiency; NE, Nanoemulsion; Nanoemulsion; Nanoemulsion-gel; PBS, phosphate buffered solution; PDI, Polydispersity Index; RI, Refractive index; SEM, Scanning Electron Microscope; TEM, Transmission Electron Microscope; Transdermal delivery; UHPLC-MS/MS, Ultra high performance liquid chromatography mass spectroscopy and mass spectroscopy; ZP, Zeta Potential.