dc.creatorIgartúa, Daniela Edith
dc.creatorMartinez, Carolina Soledad
dc.creatorTemprana, Carlos Facundo
dc.creatorAlonso, Silvia del Valle
dc.creatorPrieto, María Jimena
dc.date2018
dc.date2020-06-16T19:21:27Z
dc.date.accessioned2023-07-14T20:09:53Z
dc.date.available2023-07-14T20:09:53Z
dc.identifierhttp://sedici.unlp.edu.ar/handle/10915/98341
dc.identifierhttps://ri.conicet.gov.ar/11336/86372
dc.identifierissn:0378-5173
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/7438153
dc.descriptionCarbamazepine (CBZ) is an antiepileptic drug, which also could be used in the treatment of neurodegenerative diseases, such as the Alzheimer's disease. However, its use has been limited due to its low solubility, inefficient pharmacokinetic profiles, and multiple side effects. PAMAM dendrimers, ethylenediamine core, generation 4.0 (amine terminal groups) and 4.5 (carboxylate terminal groups) (DG4.0 and DG4.5 respectively) are polymers that can increase drug solubility through complexation. Thus, the aim of this work was to obtain and characterize complexes between CBZ and dendrimers. Both DG4.0 and DG4.5 allowed the incorporation of ∼20 molecules of CBZ per dendrimer, into their hydrophobic pockets. DG4.0-CBZ and DG4.5-CBZ complexes were found to be stable for 90 days at 37 °C and resistant to a lyophilization process, presenting controlled drug release. Also, the complexes nanotoxicity was tested ex vivo (human red blood cells), in vitro (N2a cell line), and in vivo (zebrafish). No hemolytic effect was observed in the ex vivo model. As regards in vitro toxicity, the DG4.5-CBZ complexes significantly reduced the toxicity caused by the free drug. Moreover, the DG4.5-CBZ did not cause neurotoxicity or cardiotoxicity in zebrafish larvae. In conclusion, a stable and biocompatible drug delivery system based on the DG4.5 capable of complex the CBZ has been developed. This achievement highlights the advantages of using negatively charged dendrimers for nanomedicine.
dc.descriptionInstituto Multidisciplinario de Biología Celular
dc.formatapplication/pdf
dc.format191-202
dc.languageen
dc.rightshttp://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 2.5 Argentina (CC BY-NC-SA 2.5)
dc.subjectBiología
dc.subjectCiencias Naturales
dc.subjectCarbamazepine
dc.subjectComplexation
dc.subjectEpilepsy
dc.subjectNeurodegenerative disease
dc.subjectPamam dendrimers
dc.subjectToxicology
dc.titlePAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases : A biophysical and nanotoxicological characterization
dc.typeArticulo
dc.typePreprint


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