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Preparation, Optimization, and Evaluation of Methoxy Poly(ethylene glycol)-co-Poly(ε-caprolactone) Nanoparticles Loaded by Rivastigmine for Brain Delivery
journal contribution
posted on 2020-02-21, 19:05 authored by Hamed Mohamadpour, Amir Azadi, Kobra Rostamizadeh, Sina Andalib, Mohammad Reza Saghatchi Zanjani, Mehrdad HamidiThe
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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Keywords
IV administrationdrug solutionintegration plotMPEG-PCL NPsDSC analysesBrain DeliveryHPLC-DAD methodRiv-NPs drug delivery systemMorris water maze testoptimized Riv-NPsring-opening polymerizationε- caprolactonedrug carrierAFMrelease behaviorpharmacodynamic studiesoptimized formulationnanoprecipitation methodparticle sizepharmacokinetic studyneuropharmacokinetic studyDLresponse surface D-optimal designbrain uptake clearancedrug loadingPSbrain drug deliverymemory loss
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