Complexes of Indomethacin with 4-Carbomethoxy-pyrrolidone PAMAM Dendrimers Show Improved Anti-inflammatory Properties and Temperature-Dependent Binding and Release Profile

Molecular Pharmaceutics
Mario FickerJørn B Christensen

Abstract

COX-2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common treatment for chronic inflammatory diseases like arthritis and atherosclerosis. However, they are associated with severe side effects such as cardiovascular events or stomach bleeding, due to coinhibition of other enzymes (COX1) and off-target accumulation. PAMAM dendrimers can solubilize lipophilic drugs and increase their circulation time; furthermore, PAMAM dendrimers seem to have some accumulation in inflammatory sides. Three different generations of 4-carbomethoxypyrrolidone (Pyr) surface-modified PAMAM dendrimers were complexed with the NSAID drug indomethacin, and their in-solution thermodynamic profiles were studied by means of NMR experiments. The binding stoichiometry was found dependent on solvent system and dendrimer generation. Larger dendrimers (G3-Pyr) were found to bind indomethacin through entropy driven binding mode, while G1-Pyr and G2-Pyr expressed an enthalpy driven complex formation, which means that the binding constants have a generational temperature dependency. G1/2-Pyr showed reduced binding with increasing temperature, which could be important for drug release at inflammatory sites, which have, in general, elev...Continue Reading

References

Jul 2, 1999·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·I J FranklinJ T Powell
Apr 16, 2002·Science·Ruslan Medzhitov, Charles A Janeway
Jul 26, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Abhay S ChauhanPrakash V Diwan
Dec 7, 2007·Drug Discovery Today·Teófilo VasconcelosPaulo Costa
May 27, 2008·Biomaterials·Omathanu P PerumalRangaramanujam M Kannan
Jan 16, 2010·Science·Akiko Iwasaki, Ruslan Medzhitov
May 4, 2010·International Journal of Pharmaceutics·Keerti JainN K Jain
Jul 27, 2011·TheScientificWorldJournal·Myriam HayderRémy Poupot
Nov 9, 2011·Nature Medicine·Christian Weber, Heidi Noels
Mar 17, 2012·The Journal of Physical Chemistry. B·Vishal MaingiPrabal K Maiti
Apr 25, 2012·Annual Review of Biomedical Engineering·Alexandre AlbaneseWarren C W Chan
May 1, 2012·Nanomedicine : Nanotechnology, Biology, and Medicine·Michal CiolkowskiMaria Bryszewska
Nov 14, 2013·The Journal of Physical Chemistry. B·Jon S HansenJørn B Christensen
Dec 3, 2014·Nanomedicine : Nanotechnology, Biology, and Medicine·Anna JanaszewskaBarbara Klajnert-Maculewicz
Feb 6, 2015·Bioconjugate Chemistry·Lin-Ping WuSeyed Moein Moghimi
Nov 23, 2015·Colloids and Surfaces. B, Biointerfaces·P ChanphaiH A Tajmir-Riahi

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Apr 5, 2020·Nanoscale Research Letters·Yang LiuWei Shi
Jan 12, 2021·Advanced Drug Delivery Reviews·Jun ChenHo-Wook Jun

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