5-Fluorouracil-Loaded Hyaluronic Acid-Coated Niosomal Vesicles: Fabrication and Ex Vivo Evaluation for Skin Drug Delivery

Wardah Khalid; Kifayat Ullah Shah; Muhammad Danish Saeed; Asif Nawaz; Fazal Ur Rehman; Muhammad Shoaib; Maqsood Ur Rehman; Abdullah F Alasmari; Metab Alharbi; Fawaz Alasmari

doi:10.1021/acsomega.3c04457

5-Fluorouracil-Loaded Hyaluronic Acid-Coated Niosomal Vesicles: Fabrication and Ex Vivo Evaluation for Skin Drug Delivery

ACS Omega. 2023 Nov 27;8(48):45405-45413. doi: 10.1021/acsomega.3c04457. eCollection 2023 Dec 5.

Affiliations

¹ Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Khyber Pakhtunkhwa, Pakistan.
² Department of Basic Veterinary Sciences, Gomal University, Dera Ismail Khan 29050, Khyber Pakhtunkhwa, Pakistan.
³ Department of Pharmaceutics, School of Pharmacy, University College London, 23-39 Brunswick Square, London WC1N 1AX, U.K.
⁴ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

5-Fluorouracil (5-FU) is one of the most potent drugs against solid tumors. However, its parenteral administration is associated with systemic toxicity, while its topical application has limited percutaneous absorption. To overcome these limitations, the current study undertakes the formulation of 5-FU as niosomal vesicles that were coated with hyaluronic acid to improve its targeting efficiency for cancer cells. The niosomes were prepared by the thin-film hydration method using cholesterol as physiological lipid and nonionic surfactants (Tween 80 and Span 80) in the ratio of 1:1. The niosomal vesicles were characterized for their size, size distribution, viscosity, surface tension, density, and drug entrapment efficiency. The vesicles were within the particle size range of 337-478 nm with relatively homogeneous particle size distribution (PDI ≤ 0.5). The ζ-potential and drug entrapment efficiency of coated formulations (F2 and F4) were comparatively higher than corresponding noncoated formulations (F1 and F3). The release behavior of 5-FU from niosomal vesicles using a dialysis membrane depicts that initial burst drug release was higher for F1 and F3 due to their smaller particle size in comparison to their coated counterparts. However, the release was more controlled for F4 due to the larger particle size, higher viscosity, and entrapped fraction of the formulation. The permeation of the drug through the rat's skin was comparatively higher in the case of noncoated formulations than their coated counterparts (p ≤ 0.05). This could be attributed to their small particle size and lower surface tension. In the case of coated formulations, the hydrophilic hyaluronic acid hinders the permeation of the drug through the lipid bilayer membrane of the skin. The retention of the drug in the skin was found to be in the range of 20-40%, which is sufficient to achieve optimum drug concentration in the tumorous tissue. Overall, the study successfully designed novel niosomal carrier systems for improved 5-FU delivery after topical application.