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.

Graphical Abstract

A schematic review of PEGylation, antibody conjugation, evaluation of in vitro cellular uptake, and in vivo brain uptake of antibody-targeted SLNs. The image provides the confocal microscopy image of the cellular uptake of targeted SLNs by U-87 MG (A) and the in vivo image of targeted SLN brain uptakes (B).

Keywords:

• Solid lipid nanoparticles
• methylprednisolone
• anti-Contactin-2 antibody
• anti-Neurofascin antibody
• central nervous system

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.