Intranasal teriflunomide-loaded lipid-based nanocarriers an improved remyelination potential in multiple Sclerosis: In-vitro, pharmacological, and toxicological assessments

Abstract

A potential risk of demyelination is the manifestation of autoimmune disorders affecting the central nervous system, which leads to neurodegeneration and neuropsychiatric complications in patients. Conventional delivery approaches for therapeutics in brain disorders face limitations imposed by the blood-brain barrier. It is crucial to explore biomedical applications of nanoemulsion and understand the interaction between protein-drug-loaded nanoemulsions and their targeted effect on cellular receptors. Hence, the targeted efficacy of protein bovine serum albumin (BSA) with teriflunomide (TFM) on activated microglia was estimated through a virtual molecular docking technique. Results affirm that the combination of BSA and TFM successfully targets activated microglia. Hence, this study was undertaken to formulate TFM nanoemulsion-loaded with BSA and chitosan (CH) nanocarriers (TFM-BSA-CH-NCs) and investigate their therapeutic efficacy in multiple sclerosis through intranasal delivery. TFM-BSA-CH-NCs were then assessed for globule size, ζ-potential, %EE, viscosity, and ex-vivo mucoadhesive strength, and results were found as 92.2 ± 4.0 nm, +18.3 ± 0.8 mV, 98.8 ± 0.3 %, 17.4 ± 1.2 cP, and 10.7 ± 0.3 g, respectively. TFM-BSA-CH-NCs showed sustained release and followed the Hixon-Crowel cube root model. Further, rapid remyelination was obtained in cuprizone-induced demyelinating animals after being treated with TFM-BSA-CH-NCs, which proved its efficacy. However, TFM-BSA-CH-NCs reduced the hepatotoxic potential of TFM as well as maintained TNF-α, IL-1β, GFAP, and GABA levels in experimental animals. Therefore, intranasal TFM-BSA-CH-NCs is applicable to overcome the limitations of conventional therapy and improve therapeutic potential in multiple sclerosis patients.