In vitro and in vivo assessment of the bioavailability and efficacy of carvedilol-loaded novasomes as a therapy for diabetes mellitus-associated ischemic stroke.

Abstract

Ischaemic stroke (IS) occurs when there is a deprivation of oxygen and nutrients in brain tissue. Diabetes mellitus (DM) is recognised as a possible factor contributing to this illness. Carvedilol exhibits anti-stroke effects; however, its insolubility and short half-life contribute to its ineffectiveness. The goal of this study was to create carvedilol-novasomes (CNF) nanovesicles for nasal spray as a potential DM-associated IS treatment that would increase sustainability, bioavailability, targeting and effectiveness of carvedilol. To optimise different CNF formulations, the Box-Behnken design was utilised. The optimal CNF formulation underwentevaluation in an experimental rat model of DM-associated IS. The optimal CNF formulation enhanced sustainability, bioavailability and permeability of carvedilol by 71.93%, 5.79-fold and 7.30-fold, respectively. The optimal CNF demonstrated anti-ischaemic effects by significantly enhancing various measures, including flexion, spontaneous motor activity, grip strength and target quadrant location time, with improvements of 93.72%, 88.53%, 96.57% and 353%, respectively, in comparison to the positive control group. The optimal CNF also improved the drug's targeting to the brain. These results indicate that a nasal spray formulation of the optimal CNF could serve as a promising therapy for DM-associated IS.