Effect of cholesterol-poly(N,N-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes

The development of new polymer–liposome complexes (PLCs) as delivery systems is the key issue of this work. Three main areas are dealt with: polymer synthesis/characterization, liposome formulation/characterization and evaluation of the PLCs uptake by eukaryotic cells. Poly(N,N-dimethylaminoethyl me...

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Detalles Bibliográficos
Autores principales: Alves, P., Hugo, Ayelén Amelia, Tymczyszyn, Emma Elizabeth, Ferreira, A. F., Fausto, Rui, Pérez, Pablo Fernando, Coelho, J. F. J., Simões, P. N., Gómez-Zavaglia, Andrea
Formato: Articulo
Lenguaje:Inglés
Publicado: 2013
Materias:
Química
Biología
CHO-PDMAEMA
Polymer–lipid complexe
Stimuli responsive-liposome
CF release
Cytotoxicity
Liposome internalization
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/128180
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-128180
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
Biología
CHO-PDMAEMA
Polymer–lipid complexe
Stimuli responsive-liposome
CF release
Cytotoxicity
Liposome internalization
spellingShingle Química
Biología
CHO-PDMAEMA
Polymer–lipid complexe
Stimuli responsive-liposome
CF release
Cytotoxicity
Liposome internalization
Alves, P.
Hugo, Ayelén Amelia
Tymczyszyn, Emma Elizabeth
Ferreira, A. F.
Fausto, Rui
Pérez, Pablo Fernando
Coelho, J. F. J.
Simões, P. N.
Gómez-Zavaglia, Andrea
Effect of cholesterol-poly(N,N-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes
topic_facet Química
Biología
CHO-PDMAEMA
Polymer–lipid complexe
Stimuli responsive-liposome
CF release
Cytotoxicity
Liposome internalization
description The development of new polymer–liposome complexes (PLCs) as delivery systems is the key issue of this work. Three main areas are dealt with: polymer synthesis/characterization, liposome formulation/characterization and evaluation of the PLCs uptake by eukaryotic cells. Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with low molecular weight and narrow polydispersity was synthesized by Atom Transfer Radical Polymerization (ATRP). The polymers were synthesized using two different bromide initiators (cholesteryl-2-bromoisobutyrate and ethyl 2-bromoisobutyrate) as a route to afford PDMAEMA and CHO-PDMAEMA. Both synthesized polymers (PDMAEMA and CHO-PDMAEMA) were incorporated in the preparation of lecithin liposomes (LEC) to obtain PLCs. Three polymer/lipid ratios were investigated: 5, 10 and 20%. Physicochemical characterization of PLCs was carried out by determining the zeta potential, particle size distribution, and the release of fluorescent dyes (carboxyfluorescein CF and calcein) at different temperatures and pHs. The leakage experiments showed that CHO covalently bound to PDMAEMA strongly stabilizes PLCs. The incorporation of 5% CHO-PDMAEMA to LEC (LEC_CHO-PD5) appeared to be the stablest preparation at pH 7.0 and at 37 °C. LEC_CHO-PD5 destabilized upon slight changes in pH and temperature, supporting the potential use of CHO-PDMAEMA incorporated to lecithin liposomes (LEC_CHO-PDs) as stimuli-responsive systems. In vitro studies on Raw 264.7 and Caco-2/TC7 cells demonstrated an efficient incorporation of PLCs into the cells. No toxicity of the prepared PLCs was observed according to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. These results substantiate the efficiency of CHO-PDMAEMA incorporated onto LEC to assist for the release of the liposome content in mildly acidic environments, like those found in early endosomes where pH is slightly lower than the physiologic. In summary, the main achievements of this work are: (a) novel synthesis of CHO-PDMAEMA by ATRP, (b) stabilization of LEC by incorporation of CHO-PDMAEMA at neutral pH and destabilization upon slight changes of pH, (c) efficient uptake of LEC_CHO-PDs by phagocytic and non-phagocytic eukaryotic cells.
format Articulo
Articulo
author Alves, P.
Hugo, Ayelén Amelia
Tymczyszyn, Emma Elizabeth
Ferreira, A. F.
Fausto, Rui
Pérez, Pablo Fernando
Coelho, J. F. J.
Simões, P. N.
Gómez-Zavaglia, Andrea
author_facet Alves, P.
Hugo, Ayelén Amelia
Tymczyszyn, Emma Elizabeth
Ferreira, A. F.
Fausto, Rui
Pérez, Pablo Fernando
Coelho, J. F. J.
Simões, P. N.
Gómez-Zavaglia, Andrea
author_sort Alves, P.
title Effect of cholesterol-poly(N,N-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes
title_short Effect of cholesterol-poly(N,N-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes
title_full Effect of cholesterol-poly(N,N-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes
title_fullStr Effect of cholesterol-poly(N,N-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes
title_full_unstemmed Effect of cholesterol-poly(N,N-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes
title_sort effect of cholesterol-poly(n,n-dimethylaminoethyl methacrylate) on the properties of stimuli-responsive polymer liposome complexes
publishDate 2013
url http://sedici.unlp.edu.ar/handle/10915/128180
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