title: Solid lipid nanoparticles surface modified with anti-Contactin-2 or anti-Neurofascin for brain-targeted delivery of medicines.
abstract: Multiple sclerosis (MS) is a chronic central nervous system (CNS) inflammation. Efficient drug delivery to brain is however hampered by blood-brain barrier (BBB). In order to have highly efficient and safe delivery of drugs to brain, solid lipid nanoparticles (SLNs) have indicated promising potentials as smart carriers that can pass the blood-brain barrier and deliver therapeutic biomolecules to the brain. In this study, PEGylated SLNs surface modified using anti-Contactin-2 or anti-Neurofascin, two axo-glial-glycoprotein antigens located in node of Ranvier, were prepared. These targeting moieties are considered as the main targets of autoimmune reaction in MS. The targeted SLNs were then characterized and their in vitro release profile together with their cell viability and uptake were studied. Their brain uptakes were also probed following injections in MS-induced mice. It was found that the targeted PEGylated SLNs had no significant cytotoxicity on U87MG cells although their cellular uptake was increased 4- and 8-fold when surface modified with anti-Contactin-2 or anti-Neurofascin, respectively, compared to control. Brain uptake results demonstrated higher uptake of surface-modified SLNs in the brain tissue compared with the PEGylated SLNs. The results of this report will help scientist to design more efficient nanocarriers for treatment of MS.
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Nargess
authors: N
authors: Gandomi
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|b Nanotechnology Research Centre, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Reyhaneh
authors: R
authors: Varshochian
authors: b Nanotechnology Research Centre, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|c Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Fatemeh
authors: F
authors: Atyabi
authors: b Nanotechnology Research Centre, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|d Department of Toxicology and Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Mohammad Hossein
authors: MH
authors: Ghahremani
authors: d Department of Toxicology and Pharmacology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Mohammad
authors: M
authors: Sharifzadeh
authors: e Department of Medicinal Chemistry, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Mohsen
authors: M
authors: Amini
authors: a Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|b Nanotechnology Research Centre, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors: Rassoul
authors: R
authors: Dinarvand
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D058969:Contactin 2 / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors*; D013499:Surface Properties
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D058969:Contactin 2; D004337:Drug Carriers; C054305:NFASC protein, human; D009414:Nerve Growth Factors; D008775:Methylprednisolone
keywords: Solid lipid nanoparticles; anti-Contactin-2 antibody; anti-Neurofascin antibody; central nervous system; methylprednisolone