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Dendrimer Donepezil Conjugates for Improved Brain Delivery and Better in Vivo Pharmacokinetics

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In neurodegenerative disorders, crossing the blood-brain barrier to achieve higher brain uptake of drugs has attracted considerable interest of researchers in recent years. The present approach is designed with a… Click to show full abstract

In neurodegenerative disorders, crossing the blood-brain barrier to achieve higher brain uptake of drugs has attracted considerable interest of researchers in recent years. The present approach is designed with a hypothesis that polyamidoamine (PAMAM) dendrimer can be suitable for better brain delivery of donepezil (DZ) utilizing the conjugation strategy. Amine-terminated 4.0 G PAMAM dendrimers (utilizing ethylenediamine core) were synthesized and characterized by different spectroscopic methods (1H and 13C NMR, UV–vis, Fourier transform infrared, electrospray ionization mass). The synthesized PAMAM dendrimer was then conjugated with DZ-ester and finally DZ (ester)-PAMAM conjugate (PDZ) was prepared. The chemical shifts of −CHO (δ = 9.92) and O–CH3 (δ = 3.153) in 1H NMR spectrum confirmed the synthesis of PDZ. The percent drug conjugation of DZ was approximately 26%, and 16 DZ molecules were conjugated with each PAMAM molecule. The size and ζ-potential observed of PDZ conjugate were 122 ± 1.88 nm and 0.43...

Keywords: donepezil conjugates; brain delivery; dendrimer donepezil; brain

Journal Title: ACS Omega
Year Published: 2019

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