Work

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

Year: 2025

Type: article

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.

Source: Future Journal of Pharmaceutical Sciences

DOI: 10.1186/s43094-025-00809-3