Enhancing therapeutic efficacy of Fingolimod via Intranasal Delivery in an Ethidium Bromide-induced Model of Multiple Sclerosis.

Abstract

Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological characterized by muscle weakness, numbness, tingling, vision problems, and difficulty in coordination and balance caused by the damage of myelin content around the nerve fibres. The recent literature is evident that along with their lymphocyte attack prevention mechanism, fingolimod (FNG) can serve as neuroprotective also by ensuring their improved brain availability. Therefore, in this project brain availability of FNG was enhanced by delivering the FNG in the form of nanoparticles.

New methods: Fingolimod-loaded solid lipid nanoparticles (FNG-SLNs) were prepared using the solvent evaporation method and formulation factors (lipid concentration; X1, speed; X2, surfactant concentration; X3) and response were established by factorial design. FNG-SLNs were characterized for particle size, entrapment efficiency and in-vitro drug release. Optimized formulations were characterized for in-vivo efficacy study in ethidium bromide-induced MS rat model.

Result: Obtained data revealed that the particle size and entrapment efficiency of FNG-SLNs optimized formulation was 125.4nm and 79.86% w/w respectively. In-vitro drug release study showed an initial burst release of the FNG up to 32.52% in 30min followed by sustained drug release up to 78.22% in 24h. Furthermore, in-vivo data of FNG-SLNs on ethidium bromide-induced MS rat model revealed better treatment response by showing several evidence such as signs of remyelination, restoration of neuron shape, and the recovered oligodendrocytes.

Comparison with existing methods: To the best of our knowledge this article demonstrates improved efficacy of FNG using SLNs.

Conclusion: This study demonstrates the successful development of FNG-SLNs to enhance the therapeutic efficacy of FNG for the treatment of multiple sclerosis.