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Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery

Authors Xie L, Ding X, Budry R, Mao G

Received 12 January 2018

Accepted for publication 9 March 2018

Published 31 August 2018 Volume 2018:13 Pages 4943—4960

DOI https://doi.org/10.2147/IJN.S162353

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Eytan Klausner

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster


Lingxiao Xie, Xiong Ding, Rachel Budry, Guangzhao Mao

Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI, USA

Background: The layer-by-layer (LbL) assembly method offers a molecular level control of the amount and spatial distribution of bioactive molecules. However, successful clinical translation of LbL film technology will most certainly require a better understanding and control of not only the film assembly process, but also film disassembly kinetics in physiologic conditions.
Purpose: This work focuses on the understanding and control of degradation properties of LbL films for localized gene delivery.
Methods: Bioreducible poly(amido amine)s (PAAs) containing cystaminebisacrylamide (CBA), methylenebisacrylamide, and 5-amino-1-pentanol (APOL) were synthesized by Michael addition polymerization for the construction of bioreducible LbL films capable of sequential gene delivery.
Results: The synthesized PAAs were screened for desirable buffering capacity, cell transfection, and cytotoxicity characteristics together with 25 kDa branched polyethylenimine (PEI) and cross-linked 800 Da PEI. By screening the various polycations we were able to identify a copolymer of CBA and APOL for the subsequent construction of the LbL films. By incorporating a highly transfecting polycation and a nondiffusing polycation we were able to improve the overall transfection of HEK293 and MC3T3 cells from the bioreducible LbL films. We also demonstrated the dual-stage release and transfection of two different DNAs from the LbL films.
Conclusion: The results indicate that LbL films consisting of bioreducible PAAs and non-diffusing polyelectrolytes have excellent degradation properties for the development of LbL coating technology for localized gene delivery applications.

Keywords:
biodegradable polymers, cell transfection, interlayer diffusion, localized gene delivery, polyelectrolyte multilayers, sequential release

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