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Layer-by-layer DNA films incorporating highly transfecting bioreducible poly(amido amine) and polyethylenimine for sequential gene delivery
- Source :
- International Journal of Nanomedicine
- Publication Year :
- 2018
- Publisher :
- Dove Press, 2018.
-
Abstract
- 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
- Subjects :
- polyelectrolyte multilayers
Biophysics
Pharmaceutical Science
Bioengineering
Biocompatible Materials
02 engineering and technology
sequential release
Gene delivery
010402 general chemistry
Microscopy, Atomic Force
Transfection
01 natural sciences
Time-Lapse Imaging
localized gene delivery
Biomaterials
chemistry.chemical_compound
Mice
interlayer diffusion
International Journal of Nanomedicine
Drug Discovery
Copolymer
Polyamines
Animals
Humans
Polyethyleneimine
Particle Size
Original Research
Polyethylenimine
cell transfection
Cell Death
Organic Chemistry
Layer by layer
General Medicine
DNA
021001 nanoscience & nanotechnology
Biodegradable polymer
Combinatorial chemistry
Polyelectrolytes
Polyelectrolyte
0104 chemical sciences
Solutions
HEK293 Cells
chemistry
Polymerization
biodegradable polymers
Hydrodynamics
NIH 3T3 Cells
0210 nano-technology
Subjects
Details
- Language :
- English
- ISSN :
- 11782013
- Database :
- OpenAIRE
- Journal :
- International Journal of Nanomedicine
- Accession number :
- edsair.doi.dedup.....8dbff9ecd1cb9a4ff5ff2ccb6b8910cd