Terpene-augmented novasomal gels for the sustainment of rasagiline mesylate delivery; A new approach for treating Parkinson's disease induced by rotenone in rats

Abstract

Rasagiline mesylate (RSM) is a potent anti-Parkinson's Disease (PD) drug; nevertheless, it has limited oral bioavailability due to hepatic first pass metabolism. RSM is a highly hydrophilic drug hurdled by several barriers to reach the central nervous system (CNS). This study aimed to prepare RSM-loaded novasomal gels for the transdermal delivery of the drug to CNS. Novasomes were prepared by ethanol injection method using terpenes as penetration enhancers. Design Expert® software was applied to select the optimum formulation by varying the type of terpene, amount of cholesterol, besides surface active agents (SAA): free fatty acid (FFA) ratio. The desirability calculations revealed that the optimum formulation composed of cholesterol (60 mg), SAA:FFA ratio (1:1) in the presence of eugenol. Particle size, zeta potential and entrapment efficiency of the optimum formulation were 265.90 ± 2.40 nm, −33.45 ± 0.49 mV and 83.09 ± 0.42%, respectively. TEM showed spherical well-defined nanovesicles. The optimum novasomal formulation was incorporated into gel system composed of 2% HPMC and 2% CMC. In vivo study revealed the feasibility of reversing PD symptoms regarding the behavioral, biochemical and histopathological analyses in rotenone-induced Parkinsons' rat model. A marked elevation in the number of crossovers, grooming score, frequency of rearing, gripe strength, and dopamine level besides a reduction in interleukin-17 and NLRP-3 inflammasome level when compared to positive control group were detected. No histopathological alterations were detected in examined brain sections of treated rats. In conclusion, the obtained results suggest that RSM-loaded novasomal gel formulations are promising carriers for the transdermal delivery of hydrophilic drugs like RSM.