title: Improved brain delivery of vincristine using dextran sulfate complex solid lipid nanoparticles: optimization and in vivo evaluation.
abstract: Vincristine (VC) sulfate, a freely water-soluble cytotoxic agent was incorporated into cetyl palmitate solid lipid nanoparticles (SLNs) with the aid of dextran sodium sulfate (DS), a poly anion, using a microemulsion method. The manufacturing process was optimized using response surface methodology (Box-Behnken design). SLNs were characterized for size, zeta potential, morphology, crystallinity, and release behavior. The drug encapsulation efficiency reached up to 93% and release study revealed sustained drug release. SLN formulation showed comparable cytotoxic effect in comparison to VC sulfate solution against the MDA-MB-231 cells. The in vivo studies following injection to rat revealed higher plasma and tissue concentrations and longer drug mean residence times compared to VC solution. Using cumarin-6 as a model drug, it was shown that drug delivery to the brain was enhanced close to five times using SLNs prepared in this study compared to free cumarin-6. It can be concluded that complexes of cetyl palmitate SLNs with DS could produce high VC-loaded SLNs suitable for delivery of anticancer drugs to brain tumors.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Aboutaleb
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khoshayand
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Vatanara
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.forename: Farzad
authors.initials: F
authors.lastname: Kobarfard
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D016264:Dextran Sulfate; D006801:Humans; D053758:Nanoparticles; D033362:Powder Diffraction; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D014750:Vincristine / Q000008:administration & dosage*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D016264:Dextran Sulfate
keywords: brain delivery; counter ion; cytotoxicity; dextran sulfate; solid lipid nanoparticles; vincristine