title: Brain targeting effect of camptothecin-loaded solid lipid nanoparticles in rat after intravenous administration.
abstract: This study intended to investigate the ability of solid lipid nanoparticles (SLN) to deliver camptothecin into the brain parenchyma after crossing the blood-brain barrier. For that purpose, camptothecin-loaded SLN with mean size below 200 nm, low polydispersity index (<0.25), negative surface charge (-20 mV), and high camptothecin association efficiency (>94%) were produced. Synchrotron small and wide angle X-ray scattering (SAXS/WAXS) analysis indicates that SLN maintain their physical stability in contact with DMPC membrane, whereas SLN change the lamellar structure of DMPC into a cubic phase, which is associated with efficient release of the incorporated drugs. Cytotoxicity studies against glioma and macrophage human cell lines revealed that camptothecin-loaded SLN induced cell death with the lowest maximal inhibitory concentration (IC50) values, revealing higher antitumour activity of camptothecin-loaded SLN against gliomas. Furthermore, in vivo biodistribution studies of intravenous camptothecin-loaded SLN performed in rats proved the positive role of SLN on the brain targeting since significant higher brain accumulation of camptothecin was observed, compared to non-encapsulated drug. Pharmacokinetic studies further demonstrated lower deposition of camptothecin in peripheral organs, when encapsulated into SLN, with consequent decrease in potential side toxicological effects. These results confirmed the potential of camptothecin-loaded SLN for antitumour brain treatments.
authors.affiliation: Laboratory of Pharmaceutical Technology/Centre of Research in Pharmaceutical Sciences (LTF/CICF), University of Porto, Porto, Portugal; Department of Physics and Chemistry, University of Southern Denmark, Odense M, Denmark. Electronic address: martins@sdu.dk.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Martins
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.forename: Cláudia
authors.initials: C
authors.lastname: Nunes
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
authors.forename: Domingos C
authors.initials: DC
authors.lastname: Ferreira
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D053838:Scattering, Small Angle; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008055:Lipids; D002166:Camptothecin
keywords: 1,2-dimyristoyl-sn-glycero-3-phospho-choline; Apo E; Biodistribution; Brain targeting; CNS; Camptothecin; Cytotoxicity; DMEM; DMPC; DMPC membrane bilayer model; Dulbecco’s Modified Eagle’s Medium; FBS; Gliomas; HBSS; Hanks’ Balanced Salt solution; LDL; PBCA; Polysorbates; SAXS/WAXS; SEM; SLN; Solid lipid nanoparticles (SLN); apolipoprotein E; central nervous system; fetal bovine serum; low-density lipoprotein; polybutylcyanoacrylate; scanning electron microscopy; solid lipid nanoparticles; synchrotron small and wide angle X-ray scattering