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Polymeric gene carriers bearing pendant β-cyclodextrin: the relevance of glycoside permethylation on the “in vitro” cell response

Redondo, Juan Alfonso
; 
Martínez-Campos, Enrique
; 
Plet, Laetitia
; 
Pérez-Perrino, Mónica
; 
Navarro, Rodrigo
; 
Corrales, Guillermo
; 
Pandit, Abhay
; 
Reinecke, Helmut
; 
Gallardo, Alberto
; 
López-Lacomba, José Luis
... show 2 more
Repository DOI
Publication Date
2016-02-02
Keywords
cationic polymers, cyclodextrins, gene therapy, nonviral gene vectors, polyamidoamine dendrimer, alpha-cyclodextrin, delivery vectors, gamma-cyclodextrins, cationic polymers, click clusters, transfection, pyrrolidine, therapy, cholesterol
Type
Article
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Citation
Redondo, Juan Alfonso; Martínez-Campos, Enrique; Plet, Laetitia; Pérez-Perrino, Mónica; Navarro, Rodrigo; Corrales, Guillermo; Pandit, Abhay; Reinecke, Helmut; Gallardo, Alberto; López-Lacomba, José Luis; Fernández-Mayoralas, Alfonso; Elvira, Carlos (2016). Polymeric gene carriers bearing pendant β-cyclodextrin: the relevance of glycoside permethylation on the “in vitro” cell response. Macromolecular Rapid Communications 37 (7), 575-583
Abstract
The incorporation of cyclodextrins (CDs) to nonviral cationic polymer vectors is very attractive due to recent studies that report a clear improvement of their cytocompatibility and transfection efficiency. However, a systematic study on the influence of the CD derivatization is still lacking. In this work, the relevance of beta-CD permethylation has been addressed by preparing and evaluating two series of copolymers of the cationic N-ethyl pyrrolidine methacrylamide (EPA) and styrenic units bearing pendant hydroxylated and permethylated beta-CDs (HCDSt and MeCDSt, respectively). For both cell lines, CDs permethylation shows a strong influence on plasmid DNA complexation, "in vitro" cytocompatibility and transfection efficiency of the resulting copolymers over two murine cell lines. While the incorporation of the hydroxylated CD moiety increased the cytotoxicity of the copolymers in comparison with their homopolycationic counterpart, the permethylated copolymers have shown full cytocompatibility as well as superior transfection efficiency than the controls. This behavior has been related to the different chemical nature of both units and tentatively to a different distribution of units along the polymeric chains. Cellular internalization analysis with fluorescent copolymers supports this behavior.
Funder
Publisher
Wiley-Blackwell
Publisher DOI
10.1002/marc.201500647
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)