title: 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/cm2/h) as compared with plain 5-FU gel (2.85±1.12 μg/cm2/h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm2) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm2) 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.
authors: School of Pharmacy, Taylors University; School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
authors: Paruvathanahalli Siddalingam
authors: PS
authors: Rajinikanth
authors: School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
authors: Jestin
authors: J
authors: Chellian
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D015195:Drug Design; D004890:Erythema / Q000378:metabolism / Q000517:prevention & control; D005472:Fluorouracil / Q000008:administration & dosage*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D008055:Lipids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005472:Fluorouracil
keywords: 5-fluorouracil; controlled release; nanostructured lipid carrier; skin infection; skin penetration; topical delivery