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Title

Effect on in vitro cell response of the statistical insertion of N-(2-hydroxypropyl) methacrylamide on linear pro-dendronic polyamine's gene carriers

AuthorsRedondo, J. A.; Martínez-Campos, Enrique; Navarro, Rodrigo; Reinecke, Helmut ; Elvira, Carlos ; López-Lacomba, José Luis; Gallardo Ruiz, Alberto
KeywordsDendronic
Cationic polymers
Cytocompatibility
Transfection
Statistical copolymers
HPMA
Issue Date2015
PublisherElsevier
CitationEuropean Journal of Pharmaceutics and Biopharmaceutics 93: 303-310 (2015)
AbstractStatistical copolymers of N-(2-hydroxypropyl) methacrylamide (HPMA) and the dendronic methacrylic monomer 2-(3-(Bis(2-(diethylamino)ethyl)amino)propanamido)ethyl methacrylate (TEDETAMA, derived from N,N,N′,N′-tetraethyldiethylenetriamine, TEDETA), were synthesized through radical copolymerization and evaluated in vitro as non-viral gene carriers. Three copolymers with nominal molar percentages of HPMA of 25%, 50% and 75% were prepared and studied comparatively to the positive controls poly-TEDETAMA and hyperbranched polyethyleneimine (PEI, 25 kDa). Their ability to complex DNA at different N/P molar ratios, from 1/1 up to 8/1, was determined through agarose gel electrophoresis and Dynamic Light Scattering. The resulting complexes (polyplexes) were characterized and evaluated in vitro as possible non-viral gene carriers for Swiss-3T3 fibroblasts, using luciferase as reporter gene and a calcein cytocompatibility assay. All the copolymers, except the one with highest HPMA proportion (75 molar %) at the lowest N/P ratio, condensed DNA to a particle size between 100 and 300 nm. The copolymers with 25 and 50 molar % of HPMA displayed higher transfection efficiency and cytocompatibility than the positive controls poly-TEDETAMA and PEI. A higher proportion of HPMA (75 molar %) led to copolymers that displayed very low transfection efficiency, despite their full cytocompatibility even at the highest N/P ratio. These results indicate that the statistical combination of TEDETAMA and HPMA and its fine compositional tuning in the copolymers may fulfill the fine balance of transfection efficiency and cytocompatibility in a superior way to the control poly-TEDETAMA and PEI.
URIhttp://hdl.handle.net/10261/117649
DOI10.1016/j.ejpb.2015.04.014
Identifiersdoi: 10.1016/j.ejpb.2015.04.014
issn: 0939-6411
e-issn: 1873-3441
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