title: Galactosylated nanostructured lipid carriers for delivery of 5-FU to hepatocellular carcinoma.
abstract: The aim of the present study was to design a targeted delivery system of 5-fluorouracil (5-FU) for hepatocellular carcinoma (HCC). Lactobionic acid (LB) was conjugated to stearyl amine (SA) by a chemical reaction. The nanostructured lipid carriers (NLCs), containing LB conjugate, lecithin, glyceryl monostearate, oil [oleic acid (OA) or Labrafac 5 or 10%], and 5-FU, were dissolved in alcohol/acetone, the oil phase was added to the aqueous phase containing Tween 80 or Solutol(®) HS15 (0.25 or 0.5%), and NLCs were prepared by an emulsification-solvent diffusion method. Physical properties and drug release were studied in NLCs. The thiazolyl blue tetrazolium bromide assay was used to study the cytotoxicity of NLCs on HepG(2) cells, and the cellular uptake of NLCs was determined by flow cytometry. Fourier transform infrared spectroscopy and (1)H-NMR spectra confirmed the successful conjugation of LB and SA. The optimized NLCs consisted of 0.5% Solutol HS15 and 10% OA oil. The particle size of these nanoparticles was 139.2 nm, with a zeta potential of -18 mV, loading efficiency of 34.2%, release efficiency after 2 hours of the release test was 72.6%, and crystallinity was 0.63%. The galactosylated NLCs of 5-FU were cytotoxic on the HepG(2) cell line in a half concentration of 5-FU and seems promising in reducing 5-FU dose in HCC.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. varshosaz@pharm.mui.ac.ir
authors.forename: Jaleh
authors.initials: J
authors.lastname: Varshosaz
authors.forename: Farshid
authors.initials: F
authors.lastname: Hassanzadeh
authors.forename: Hojjat
authors.initials: H
authors.lastname: Sadeghi
authors.forename: Mostafa
authors.initials: M
authors.lastname: Khadem
mesh_terms: D000096:Acetone / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage; D037263:Asialoglycoprotein Receptor / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D005690:Galactose / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D019301:Oleic Acid / Q000737:chemistry; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D018675:Toxicity Tests
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D037263:Asialoglycoprotein Receptor; D003692:Delayed-Action Preparations; D004187:Disaccharides; D004337:Drug Carriers; D005989:Glycerides; D011136:Polysorbates; D013778:Tetrazolium Salts; D013844:Thiazoles; D000096:Acetone; C048159:glyceryl monostearate; D019301:Oleic Acid; C005608:lactobionic acid; C022616:thiazolyl blue; C009317:stearylamine; D005472:Fluorouracil; D005690:Galactose