A novel 5-Fluorocuracil multiple-nanoemulsion used for the enhancement of oral bioavailability in the treatment of colorectal cancer

Niyaz Ahmad; Ahmed A Albassam; Mohd Faiyaz Khan; Zabih Ullah; Taysser Mohammed Buheazah; Hussain Salman AlHomoud; Hassan Ali Al-Nasif

doi:10.1016/j.sjbs.2022.02.017

A novel 5-Fluorocuracil multiple-nanoemulsion used for the enhancement of oral bioavailability in the treatment of colorectal cancer

Saudi J Biol Sci. 2022 May;29(5):3704-3716. doi: 10.1016/j.sjbs.2022.02.017. Epub 2022 Mar 14.

Authors

Niyaz Ahmad¹, Ahmed A Albassam², Mohd Faiyaz Khan², Zabih Ullah³, Taysser Mohammed Buheazah¹, Hussain Salman AlHomoud¹, Hassan Ali Al-Nasif¹

Affiliations

¹ Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
² Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia.
³ Department of Pharmaceutical Sciences, College of Pharmacy and Dentistry, Buraydah Colleges, Alqassim, Saudi Arabia.

Abstract

5-Fluorouracil (5-FU) is a drug of choice for colorectal-cancer. But oral therapeutic efficacy of 5-FU is restricted due to their very little bioavailability because of poor membrane permeability and GIT-absorption. We have developed a multiple nanoemulsion (w/o/w i.e. 5-FU-MNE) in which 5-FU incorporated to improve their oral-absorption. Globule-size of opt-5-FU-MNE was 51.64 ± 2.61 nm with PDI and ZP 0.101 ± 0.001 and -5.59 ± 0.94, respectively. In vitro 5-FU-release and ex vivo permeation studies exhibited 99.71% release and 83.64% of 5-FU from opt-nanoformulation. Cytotoxic in vitro studies-exhibited that 5-FU in opt-5-FU-MNE was 5-times more potent than 5-FU-S on human-colon-cancer-cell-lines (HT-29). The enhanced C_max with AUC_0-8h with opt-5-FU-MNE was shown extremely significant (p < 0.001) in wistar rat's plasma in the comparison of oral and i.v. treated group of 5-FU-S by PK-observations. Furthermore, opt-5-FU-MNE was showed much more significant (p < 0.001) results as compared to 5-FU-S (free) on cell lines for human colon cancer (HT-29).

Keywords: 5-Fluorouracil; Chemoprevention of colorectal cancer; Cytotoxic activity; Enhancement of oral bioavailability; Multiple-nanoemulsion (w/o/w); Pharmacokinetics; UHPLC-MS/MS bioanalytical-method.