title: In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting.
abstract: The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (P<0.05) increased 5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution. However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo 11790, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Nasr
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo 11790, Egypt.
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Ghorab
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo 11790, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdelazem
keywords: 5-Fluorouracil; Cubosomes; Hepatotoxicity; Hydrophilic drug; Liver targeting