TY - JOUR
T1 - Effect on in vitro cell response of the statistical insertion of N-(2-hydroxypropyl) methacrylamide on linear pro-dendronic polyamine's gene carriers
AU - Redondo, Juan Alfonso
AU - Martínez-Campos, Enrique
AU - Navarro, Rodrigo
AU - Reinecke, Helmut
AU - Elvira, Carlos
AU - López-Lacomba, José Luis
AU - Gallardo, Alberto
N1 - Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/5/26
Y1 - 2015/5/26
N2 - Statistical 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.
AB - Statistical 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.
KW - Cationic polymers
KW - Cytocompatibility
KW - Dendronic
KW - HPMA
KW - Statistical copolymers
KW - Transfection
UR - http://www.scopus.com/inward/record.url?scp=84930201670&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930201670&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2015.04.014
DO - 10.1016/j.ejpb.2015.04.014
M3 - Article
C2 - 25937440
AN - SCOPUS:84930201670
SN - 0939-6411
VL - 93
SP - 303
EP - 310
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -