Abstract
The objective of this study was to formulate and investigate the neuropharmacokinetics and pharmacodynamics of rivastigmine (Riv) loaded methoxy poly(ethylene glycol)-co-poly(ε-caprolactone) (MPEG-PCL) nanoparticles (Riv-NPs) in rats after IV administration. The MPEG-PCL was synthesized via ring-opening polymerization of ε-caprolactone by MPEG and used to prepare Riv-NPs by the nanoprecipitation method. Response surface D-optimal design was applied to optimize Riv-NPs drug delivery system. The optimized formulation showed a particle size (PS) of 98.5 ± 2.1 nm, drug loading (DL) of 19.2 ± 1.1%, and sustained release behavior of the drug. Moreover, the optimized Riv-NPs were characterized by AFM and DSC analyses. A simple and sensitive HPLC-DAD method for bioanalysis was developed and successfully applied to the pharmacokinetic study. The neuropharmacokinetic study in rats indicated that the integration plot was linear, and the brain uptake clearance of the drug-loaded in MPEG-PCL NPs was significantly higher than the free drug. Furthermore, results of pharmacodynamic studies using the Morris water maze test demonstrated faster regain of memory loss with Riv-NPs when compared to the free drug solution. The results revealed that the mentioned biodegradable nanoparticle holds promise as a suitable drug carrier for brain drug delivery.
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