Pharmacokinetic and Pharmacodynamic Studies of Prednisolone Acetate

Abstract

Prednisolone acetate (PA) is a corticosteroid with potential application in the management of multiple sclerosis; however, effective delivery to brain tissue remains challenging. The present study evaluated an optimized prednisolone acetate solid lipid nanoparticle (PA-SLN) formulation for intranasal brain-targeted delivery and compared its pharmacodynamic and pharmacokinetic performance with conventional oral PA. The optimized formulation contained 11% tristearin, 58.88% surfactant mixture [Cremophor RH40:ethanol (3:1)] and a sonication time of 9.33 min. Male mice were divided into normal, diseased, oral PA and intranasal PA-SLN groups and treated for 21 days at 1.988 mg/kg in a cuprizone-induced multiple sclerosis model. Locomotor activity and motor coordination were assessed using actophotometer, open-field, rota-rod and swim tests, while brain histopathology evaluated demyelination and remyelination. PA concentrations in plasma and brain homogenate were quantified by HPLC. Intranasal PA-SLNs significantly improved locomotor activity and motor coordination and promoted faster remyelination compared with oral treatment.