Glatiramer–diclofenac nanocomplex enhances remyelination in a mouse model of multiple sclerosis

Abstract Background The hallmark of multiple sclerosis (MS) is neuronal demyelination. Glatiramer acetate (GA) injection is used in the management of MS. Nevertheless, it suffers unacceptable adverse reactions. Alternatively, nose-to-brain drug delivery escapes the blood–brain barrier. Diclofenac sodium (DCL), a non-steroidal anti-inflammatory drug, is used in MS pain management. The current study aimed to evaluate the neuroprotective effect of a nasally administrated glatiramer–diclofenac (GA-DCL) nanocomplex formula against cuprizone (CPZ)-induced demyelination in mice. Results By using Box–Behnken design, a GA-DCL optimized nanoconjugate was characterized and formulated in gellan gum in situ gel. DCL, GA, and the optimized GA-DCL formula were administrated intra-nasally, while cuprizone (CPZ) was given orally for six weeks. All mice were subjected to behavioral, histopathological, and biochemical investigations. The optimized GA-DCL nanocomplex prepared at a molar ratio of 1:1.4 was characterized with respect to particle size (198.21 ± 11.60 nm) and zeta potential (34.53 ± 2.13 mV). GA-DCL nanocomplex showed superior neuroprotective activities than either drug alone against CPZ toxicity. This was evidenced by inhibiting CPZ-induced body weight loss, motor impairment, oxidative stress, neuronal demyelination and inflammation. Conclusion The optimized GA-DCL nasal formula exhibits higher neuroprotective activity than either drug alone in the CPZ mice model of MS. These findings warrant further experimental and clinical studies.