Lactoferrin, chitosan double-coated oleosomes loaded with clobetasol propionate for remyelination in multiple sclerosis: Physicochemical characterization and in-vivo assessment in a cuprizone-induced demyelination model.

Abdelalim, Lamiaa R; Elnaggar, Yosra S R; Abdallah, Ossama Y

Abdelalim, Lamiaa R; Elnaggar, Yosra S R; Abdallah, Ossama Y.

Afiliación

Abdelalim LR; Department of Pharmaceutics and pharmaceutical technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Elnaggar YSR; Department of Pharmaceutics and pharmaceutical technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. Electronic address: yosra.s.elnaggar@gmail.com.
Abdallah OY; Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.

Int J Biol Macromol ; 277(Pt 1): 134144, 2024 Oct.

Article en En | MEDLINE | ID: mdl-39053824

ABSTRACT

ABSTRACT

Multiple sclerosis is a chronic inflammatory demyelinating disorder of the CNS characterized by continuous myelin damage accompanied by deterioration in functions. Clobetasol propionate (CP) is the most potent topical corticosteroid with serious side effects related to systemic absorption. Previous studies introduced CP for remyelination without considering systemic toxicity. This work aimed at fabrication and optimization of double coated nano-oleosomes loaded with CP to achieve brain targeting through intranasal administration. The optimized formulation was coated with lactoferrin and chitosan for the first time. The obtained double-coated oleosomes had particle size (220.07 ± 0.77 nm), zeta potential (+30.23 ± 0.41 mV) along with antioxidant capacity 9.8 µM ascorbic acid equivalents. Double coating was well visualized by TEM and significantly decreased drug release. Three different doses of CP were assessed in-vivo using cuprizone-induced demyelination in C57Bl/6 mice. Neurobehavioral tests revealed improvement in motor and cognitive functions of mice in a dose-dependent manner. Histopathological examination of the brain showed about 2.3 folds increase in corpus callosum thickness in 0.3 mg/kg CP dose. Moreover, the measured biomarkers highlighted the significant antioxidant and anti-inflammatory capacity of the formulation. In conclusion, the elaborated biopolymer-integrating nanocarrier succeeded in remyelination with 6.6 folds reduction in CP dose compared to previous studies.

Asunto(s)

Quitosano; Clobetasol; Cuprizona; Enfermedades Desmielinizantes; Modelos Animales de Enfermedad; Lactoferrina; Esclerosis Múltiple; Remielinización; Animales; Lactoferrina/química; Lactoferrina/farmacología; Quitosano/química; Ratones; Clobetasol/farmacología; Clobetasol/química; Remielinización/efectos de los fármacos; Enfermedades Desmielinizantes/inducido químicamente; Enfermedades Desmielinizantes/tratamiento farmacológico; Enfermedades Desmielinizantes/patología; Esclerosis Múltiple/tratamiento farmacológico; Esclerosis Múltiple/inducido químicamente; Liposomas/química; Ratones Endogámicos C57BL; Masculino; Tamaño de la Partícula; Encéfalo/efectos de los fármacos; Encéfalo/patología; Encéfalo/metabolismo; Antioxidantes/farmacología; Antioxidantes/química; Liberación de Fármacos

Palabras clave

Chitosan; Clobetasol propionate; Lactoferrin; Multiple sclerosis; Oleosomes; Remyelination

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clobetasol / Enfermedades Desmielinizantes / Cuprizona / Quitosano / Modelos Animales de Enfermedad / Remielinización / Lactoferrina / Esclerosis Múltiple Límite: Animals Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Países Bajos

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