Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil

Abstract

The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol ® ATO 5 (glyceryl palmitostearate) and Labrasol ® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol ® HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol ® 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, −21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 μg/cm 2 /h) as compared with plain 5-FU gel (2.85±1.12 μg/cm 2 /h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm 2 ) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm 2 ) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations.

Nanostructured Lipid Carriers: A Groundbreaking Approach for Transdermal Drug Delivery

“…Determining the particle size is of great importance in nanostructured formulations as the small particle size contributes to a greater interfacial area, which can then provide better drug partitioning and absorption at the skin surface. [47][48][49] Zeta potential Zeta potential (ZP) is a key factor for evaluation of the stability of nano dispersion. The ZP determination is based on particle electrophoretic mobility in aqueous medium.…”

Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

“…The use of chemotherapeutic agents is a major strategy for destroying cancer cells and maintaining normal cell development in cancer patients [1]. 5-Fluorouracil (5-FU), an antimetabolic chemotherapeutic agent used mostly to treat various types of cancer and tumors, is a fluorinated pyrimidine whose anticancer activity is based on its capacity to interfere with nucleotide metabolism, as well as RNA and DNA synthesis [2][3][4][5]. However, several adverse effects are associated with 5-FU therapy, including nausea, vomiting, diarrhea, myelosuppression, and intestinal mucositis [6][7][8][9][10][11].…”

Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics

“…Furthermore, the skin retention study observed high retention of 5-Fu from NLC gel (91.256 ± 4.56 lg/cm 2 ) compared with pure drug (12.23 ± 3.86 lg/cm 2 ). Overall, results indicated that 5-fluorouracil incorporated NLC potentially delivered in skin layers with minimal irritation [81].…”