Nanoparticles from Gantrez® AN-poly(ethylene glycol) conjugates as carriers for oral delivery of docetaxel
Keywords: 
Materias Investigacion::Farmacia::Química farmacéutica
Bioavailability
Conjugates
Docetaxel
Nanoparticles
Oral delivery
Poly(ethylene glycol)
Issue Date: 
2019
Publisher: 
Elsevier BV
Publisher Version: 
ISSN: 
0378-5173
Note: 
This manuscript is distributed under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited
Citation: 
Ruiz-Gaton, L. (Luisa); Espuelas, S. (Socorro); Huarte, J. (Judit); et al. "Nanoparticles from Gantrez® AN-poly(ethylene glycol) conjugates as carriers for oral delivery of docetaxel". International Journal of Pharmaceutics. 571, 2019, 118699
Abstract
The oral delivery of docetaxel (DTX) is challenging due to a low bioavailability, related to an important pre-systemic metabolism. With the aim of improving the bioavailability of this cytotoxic agent, nanoparticles from conjugates based on the copolymer of methyl vinyl ether and maleic anhydride (poly(anhydride)) and two different types of PEG, PEG2000 (PEG2) or methoxyPEG2000 (mPEG2), were evaluated. Nanoparticles, with a DTX loading close to 10%, were prepared by desolvation and stabilized with calcium, before purification and lyophilization. For the pharmacokinetic study, nanoparticles were orally administered to mice at a single dose of 30 mg/kg. The plasma levels of DTX were high, prolonged in time and, importantly, quantified within the therapeutic window. The relative oral bioavailability was calculated to be up to 56% when DTX was loaded in nanoparticles from poly(anhydride)-mPEG2000 conjugate (DTX-NP-mPEG2). Finally, a comparative toxicity study between equitoxic doses of free iv DTX and oral DTX-NP-mPEG2 was conducted in mice. Animals orally treated with DTX-loaded nanoparticles displayed less severe signs of hypersensitivity reactions, peripheral neurotoxicity, myelosuppression and hepatotoxicity than free iv docetaxel. In summary, poly(anhydride)-PEG conjugate nanoparticles appears to be adequate carries for the oral delivery of docetaxel.

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