Effect of molecular weight of amine end-modified poly(β-amino ester)s on gene delivery efficiency and toxicity.

Biomaterials
Ahmed A EltoukhyDaniel G Anderson

Abstract

Amine end-modified poly(β-amino ester)s (PBAEs) have generated interest as efficient, biodegradable polymeric carriers for plasmid DNA (pDNA). For cationic, non-degradable polymers, such as polyethylenimine (PEI), the polymer molecular weight (MW) and molecular weight distribution (MWD) significantly affect transfection activity and cytotoxicity. The effect of MW on DNA transfection activity for PBAEs has been less well studied. We applied two strategies to obtain amine end-modified PBAEs varying in MW. In one approach, we synthesized four amine end-modified PBAEs with each at 15 different monomer molar ratios, and observed that polymers of intermediate length mediated optimal DNA transfection in HeLa cells. Biophysical characterization of these feed ratio variants suggested that optimal performance was related to higher DNA complexation efficiency and smaller nanoparticle size, but not to nanoparticle charge. In a second approach, we used preparative size exclusion chromatography (SEC) to obtain well-defined, monodisperse polymer fractions. We observed that the transfection activities of size-fractionated PBAEs generally increased with MW, a trend that was weakly associated with an increase in DNA binding efficiency. Furthermo...Continue Reading

References

Sep 19, 1998·Journal of Controlled Release : Official Journal of the Controlled Release Society·P van de WeteringW E Hennink
Jul 9, 1999·Journal of Biomedical Materials Research·W T GodbeyA G Mikos
Jan 29, 2000·Biotechnology and Bioengineering·D V SchafferD A Lauffenburger
Feb 25, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kensuke MorimotoMitsuru Hashida
May 2, 2003·Journal of the American Chemical Society·Akin AkincRobert Langer
May 3, 2003·Nature Reviews. Genetics·Clare E ThomasMark A Kay
Nov 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Daniel G AndersonJanet A Sawicki
Feb 25, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniel G AndersonRobert Langer
Mar 12, 2005·Nature Reviews. Genetics·Dominic J GloverDavid A Jans
May 21, 2005·The Journal of Gene Medicine·Miriam BreunigAchim Goepferich
Jul 30, 2005·Nature Reviews. Drug Discovery·Daniel W PackPatrick S Stayton
Apr 1, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Stephanie WerthAchim Aigner
Mar 21, 2007·Biomaterials·Sathya SrinivasachariTheresa M Reineke
Mar 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gregory T ZugatesDaniel G Anderson
Jan 19, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jordy LutenWim E Hennink
Dec 5, 2008·Chemical Reviews·Meredith A Mintzer, Eric E Simanek
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Fan YangDaniel G Anderson
Aug 20, 2011·American Journal of Public Health·Janice A Edelstein
Dec 28, 2009·Advanced Materials·Joel SunshineDaniel G Anderson

❮ Previous
Next ❯

Citations

Nov 14, 2013·Archives of Pharmacal Research·Hyun-Ji ParkSeung-Woo Cho
Apr 11, 2013·Journal of the American Chemical Society·Corey J BishopJordan J Green
Nov 21, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Allison NautaFan Yang
Apr 28, 2012·Tissue Engineering. Part B, Reviews·Xintong WangHak-Joon Sung
Aug 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Charles H JonesBlaine A Pfeifer
Oct 8, 2013·Molecular Pharmaceutics·Charles H JonesBlaine A Pfeifer
Jan 14, 2016·Expert Opinion on Biological Therapy·Jessica Pahle, Wolfgang Walther
Feb 3, 2015·ACS Nano·Antonella MangravitiJordan J Green
Aug 13, 2015·Biomacromolecules·Lara CutlarWenxin Wang
Apr 22, 2015·Angewandte Chemie·Cheol Am HongYoon Sung Nam
Apr 29, 2015·Acta Biomaterialia·Chengnan ZhangChao Lin
Sep 26, 2013·International Journal of Pharmaceutics·Hamideh ParhizMohammad Ramezani
Sep 24, 2014·Acta Biomaterialia·Corey J BishopJordan J Green
Oct 22, 2016·Angewandte Chemie·James C KaczmarekDaniel G Anderson
Mar 8, 2017·The Journal of Physical Chemistry. B·Seyoung JungTheresa M Reineke
Mar 8, 2017·ACS Applied Materials & Interfaces·Xiangang HuangBastien Castagner
Jan 11, 2018·Journal of Biomedical Materials Research. Part a·Ece AkyolDuygu Avci
Oct 3, 2018·Therapeutic Delivery·Priya Sahadevan Syamala, Rekha Mannemcherril Ramesan
Jan 5, 2019·Advanced Materials·Asha Kumari PatelDaniel G Anderson
Sep 10, 2019·Expert Opinion on Drug Delivery·David UlkoskiVenkata R Krishnamurthy
Jul 24, 2020·Expert Opinion on Drug Delivery·Johan KarlssonStephany Y Tzeng
May 14, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Bing WangXiao-Qi Yu
Nov 7, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Tatiana LovatoClaudia Conte
May 16, 2018·Advanced Healthcare Materials·Umberto Capasso PalmieroDaniel G Anderson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.