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Artículo

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization

Igartúa, DanielaIcon ; Martinez, Carolina SoledadIcon ; Temprana, Carlos FacundoIcon ; Alonso, Silvia del ValleIcon ; Prieto, Maria JimenaIcon
Fecha de publicación: 06/2018
Editorial: Elsevier Science
Revista: International Journal Of Pharmaceutics
ISSN: 0378-5173
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Biofísica

Resumen

Carbamazepine (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.
Palabras clave: CARBAMAZEPINE , COMPLEXATION , EPILEPSY , NEURODEGENERATIVE DISEASE , PAMAM DENDRIMERS , TOXICOLOGY
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/86372
DOI: http://dx.doi.org/10.1016/j.ijpharm.2018.04.032
URL: https://www.sciencedirect.com/science/article/pii/S0378517318302497
Colecciones
Articulos(CCT - LA PLATA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos(IMBICE)
Articulos de INST.MULTIDISCIPL.DE BIOLOGIA CELULAR (I)
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Citación
Igartúa, Daniela; Martinez, Carolina Soledad; Temprana, Carlos Facundo; Alonso, Silvia del Valle; Prieto, Maria Jimena; PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization; Elsevier Science; International Journal Of Pharmaceutics; 544; 1; 6-2018; 191-202
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