Combined Therapy for Alzheimer’s Disease : Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity

Alzheimer’s disease has become a public health priority, so an investigation of new therapies is required. Tacrine (TAC) was licensed for treatments; however, its oral administration caused hepatotoxicity, so it is essential to reduce the side effects. PAMAM dendrimer generation 4.0 and 4.5 (DG4.0 a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Igartúa, Daniela Edith, Gómez Martínez, Carolina, Alonso, Silvia del Valle, Prieto, María Jimena
Formato:	Articulo
Lenguaje:	Inglés
Publicado:	2020
Materias:	Biología Ciencias Exactas tacrine PAMAM dendrimers toxicology alzheimer’s disease combined therapy
Acceso en línea:	http://sedici.unlp.edu.ar/handle/10915/139237
Aporte de:	SEDICI (UNLP) de Universidad Nacional de La Plata

id	I19-R120-10915-139237
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 Exactas tacrine PAMAM dendrimers toxicology alzheimer’s disease combined therapy
spellingShingle	Biología Ciencias Exactas tacrine PAMAM dendrimers toxicology alzheimer’s disease combined therapy Igartúa, Daniela Edith Gómez Martínez, Carolina Alonso, Silvia del Valle Prieto, María Jimena Combined Therapy for Alzheimer’s Disease : Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity
topic_facet	Biología Ciencias Exactas tacrine PAMAM dendrimers toxicology alzheimer’s disease combined therapy
description	Alzheimer’s disease has become a public health priority, so an investigation of new therapies is required. Tacrine (TAC) was licensed for treatments; however, its oral administration caused hepatotoxicity, so it is essential to reduce the side effects. PAMAM dendrimer generation 4.0 and 4.5 (DG4.0 and DG4.5) can be used as drug delivery systems and as nanodrugs per se. Our work aims to propose a combined therapy based on TAC and PAMAM dendrimer co-administration. TAC and dendrimer interactions were studied by in vitro drug release, drug stability, and FTIR. The toxicity profile of co-administration was evaluated in human red blood cells, in Neuro-2a cell culture, and in zebrafish larvae. Also, the anti-acetylcholinesterase activity was studied in cell culture. It was possible to obtain DG4.0-TAC and DG4.5-TAC suspensions, without reducing the drug solubility and stability. FTIR and in vitro release studies confirmed that interaction between TAC and DG4.5 was of the electrostatic type. No toxicity effects on human red blood cells were observed, whereas the co-administration with DG4.5 reduced cytotoxicity of TAC on the Neuro-2a cell line. Moreover, in vivo co-administration of both DG4.0-TAC and DG4.5-TAC reduced the morphological and hepatotoxic effects of TAC in zebrafish larvae. The reduction of TAC toxicity was not accompanied by a reduction in its activity since the anti-acetylcholinesterase activity remains when it is co-administrated with dendrimers. In conclusion, the co-administration of TAC with both DG4.0 and DG4.5 is a novel therapy since it was less-toxic, was more biocompatible, and has the same effectiveness than the free drug.
format	Articulo Articulo
author	Igartúa, Daniela Edith Gómez Martínez, Carolina Alonso, Silvia del Valle Prieto, María Jimena
author_facet	Igartúa, Daniela Edith Gómez Martínez, Carolina Alonso, Silvia del Valle Prieto, María Jimena
author_sort	Igartúa, Daniela Edith
title	Combined Therapy for Alzheimer’s Disease : Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity
title_short	Combined Therapy for Alzheimer’s Disease : Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity
title_full	Combined Therapy for Alzheimer’s Disease : Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity
title_fullStr	Combined Therapy for Alzheimer’s Disease : Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity
title_full_unstemmed	Combined Therapy for Alzheimer’s Disease : Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity
title_sort	combined therapy for alzheimer’s disease : tacrine and pamam dendrimers co-administration reduces the side effects of the drug without modifying its activity
publishDate	2020
url	http://sedici.unlp.edu.ar/handle/10915/139237
work_keys_str_mv	AT igartuadanielaedith combinedtherapyforalzheimersdiseasetacrineandpamamdendrimerscoadministrationreducesthesideeffectsofthedrugwithoutmodifyingitsactivity AT gomezmartinezcarolina combinedtherapyforalzheimersdiseasetacrineandpamamdendrimerscoadministrationreducesthesideeffectsofthedrugwithoutmodifyingitsactivity AT alonsosilviadelvalle combinedtherapyforalzheimersdiseasetacrineandpamamdendrimerscoadministrationreducesthesideeffectsofthedrugwithoutmodifyingitsactivity AT prietomariajimena combinedtherapyforalzheimersdiseasetacrineandpamamdendrimerscoadministrationreducesthesideeffectsofthedrugwithoutmodifyingitsactivity
bdutipo_str	Repositorios
_version_	1764820457305931777

Combined Therapy for Alzheimer’s Disease : Tacrine and PAMAM Dendrimers Co-Administration Reduces the Side Effects of the Drug without Modifying its Activity

Ejemplares similares