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

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,...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Igartúa, Daniela Edith, Martinez, Carolina Soledad, Temprana, Carlos Facundo, Alonso, Silvia del Valle, Prieto, María Jimena
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2018
Materias:
Biología
Ciencias Naturales
Carbamazepine
Complexation
Epilepsy
Neurodegenerative disease
Pamam dendrimers
Toxicology
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/98341
https://ri.conicet.gov.ar/11336/86372
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-98341
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ciencias Naturales
Carbamazepine
Complexation
Epilepsy
Neurodegenerative disease
Pamam dendrimers
Toxicology
spellingShingle Biología
Ciencias Naturales
Carbamazepine
Complexation
Epilepsy
Neurodegenerative disease
Pamam dendrimers
Toxicology
Igartúa, Daniela Edith
Martinez, Carolina Soledad
Temprana, Carlos Facundo
Alonso, Silvia del Valle
Prieto, María Jimena
PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases : A biophysical and nanotoxicological characterization
topic_facet Biología
Ciencias Naturales
Carbamazepine
Complexation
Epilepsy
Neurodegenerative disease
Pamam dendrimers
Toxicology
description 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.
format Articulo
Preprint
author Igartúa, Daniela Edith
Martinez, Carolina Soledad
Temprana, Carlos Facundo
Alonso, Silvia del Valle
Prieto, María Jimena
author_facet Igartúa, Daniela Edith
Martinez, Carolina Soledad
Temprana, Carlos Facundo
Alonso, Silvia del Valle
Prieto, María Jimena
author_sort Igartúa, Daniela Edith
title PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases : A biophysical and nanotoxicological characterization
title_short PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases : A biophysical and nanotoxicological characterization
title_full PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases : A biophysical and nanotoxicological characterization
title_fullStr PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases : A biophysical and nanotoxicological characterization
title_full_unstemmed PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases : A biophysical and nanotoxicological characterization
title_sort pamam dendrimers as a carbamazepine delivery system for neurodegenerative diseases : a biophysical and nanotoxicological characterization
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/98341
https://ri.conicet.gov.ar/11336/86372
work_keys_str_mv AT igartuadanielaedith pamamdendrimersasacarbamazepinedeliverysystemforneurodegenerativediseasesabiophysicalandnanotoxicologicalcharacterization
AT martinezcarolinasoledad pamamdendrimersasacarbamazepinedeliverysystemforneurodegenerativediseasesabiophysicalandnanotoxicologicalcharacterization
AT tempranacarlosfacundo pamamdendrimersasacarbamazepinedeliverysystemforneurodegenerativediseasesabiophysicalandnanotoxicologicalcharacterization
AT alonsosilviadelvalle pamamdendrimersasacarbamazepinedeliverysystemforneurodegenerativediseasesabiophysicalandnanotoxicologicalcharacterization
AT prietomariajimena pamamdendrimersasacarbamazepinedeliverysystemforneurodegenerativediseasesabiophysicalandnanotoxicologicalcharacterization
bdutipo_str Repositorios
_version_ 1764820493003653121

Ejemplares similares