Preparation, Optimization, and Evaluation of Methoxy Poly(ethylene glycol)-co-Poly(ε-caprolactone) Nanoparticles Loaded by Rivastigmine for Brain Delivery

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.

Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval

“…Acetylcholinesterase inhibitor PEG-b-PCL The PK study in rats indicated that the brain uptake of rivastigmine-loaded micelle was significantly higher than that of the free drug. Pharmacodynamic studies using the Morris water maze test confirmed that faster regain of memory loss with micellar formulation when compared to the free drug solution [330]. .…”

Evaluation of the effects of nanoprecipitation process parameters on the size and morphology of poly(ethylene oxide)-block-polycaprolactone nanostructures

“…To allow the modelling of linear, quadratic and two-way interaction effects of each factor with a minimal amount of experimental runs, a D-optimal split-plot experimental design with three levels for each factor was created using the DoE functionality of JMP Pro 14 software (SAS). Similar approaches have been taken by several authors to optimize NP formulations (Günday Türeli, et al 2016;Mohamadpour, et al 2020;Tahir, et al 2017).…”

Management of Brain Cancer and Neurodegenerative Disorders with Polymer-Based Nanoparticles as a Biocompatible Platform

“…Changing the molar mass or coating it with alternative polymers, such as PLA, might alleviate this problem [ 111 ]. Hence, it has been used as a suitable coating in the design of the brain delivery system [ 52 , 112 , 113 ].…”