Understanding the mechanism of action of poly(amidoamine)s as endosomolytic polymers: correlation of physicochemical and biological properties

Biomacromolecules
Peter C GriffithsRuth Duncan

Abstract

Bioresponsive poly(amidoamine)s (PAA)s are currently under development as endosomolytic polymers for intracellular delivery of proteins and genes. Here for the first time, small-angle neutron scattering (SANS) is used to systematically investigate the pH-dependent conformational change of an endosomolytic polymer, the PAA ISA 23. The radius of gyration of the ISA23 was determined as a function of pH and counterion, the aim being to correlate changes in polymer conformation with membrane activity assessed using a rat red blood cell haemolysis assay. With decreasing pH, the ISA23 radius of gyration increased to a maximum (R(g) approximately 80 A) around pH = 3, before subsequently decreasing once more. At high pH and therefore high ionic strengths, the polymer is negatively charged and adopts a rather compact structure (R(g) approximately 20 A), presumably with the dissociated carboxylic groups on the exterior of the polymer coil. At low pH, the coil again collapses (R(g) < 20 A), presumably due to the effects of the high ionic strength. It is concluded that the nature of the salt form has no direct bearing on the size of the polymer coil, but it does indirectly determine the prevailing pH and, hence, polymer conformation. Pulsed...Continue Reading

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Citations

Oct 7, 2011·Molecular Pharmaceutics·Ruth Duncan, Rogerio Gaspar
Jan 31, 2006·Chemical Society Reviews·P C GriffithsN Hirst
Dec 21, 2006·The Journal of Chemical Physics·Minerva González-MelchorJosé Alejandre
Apr 23, 2009·Expert Opinion on Drug Delivery·Chao Lin, Johan F J Engbersen
May 22, 2008·Expert Opinion on Drug Delivery·María J VicentAntonio Pineda-Lucena
Oct 29, 2010·Journal of Drug Targeting·Ulrik L RahbekKenneth A Howard
Feb 1, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Grégory Coué, Johan F J Engbersen
Nov 28, 2009·Advanced Drug Delivery Reviews·Eder Lilia Romero, Maria Jose Morilla
Oct 14, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Simon C W RichardsonRuth Duncan
Aug 25, 2009·Advanced Drug Delivery Reviews·Francesca Greco, María J Vicent
Jul 29, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Chao Lin, Johan F J Engbersen
Oct 21, 2004·Macromolecular Bioscience·Nathalie LavignacRuth Duncan
Feb 9, 2008·Chemistry : a European Journal·Laura HartmannHans G Börner
Nov 20, 2008·Macromolecular Bioscience·Nathalie LavignacRuth Duncan
Jul 25, 2013·Advanced Drug Delivery Reviews·Arun K IyerMansoor M Amiji
Sep 30, 2016·Macromolecular Bioscience·Yanping SunPingtian Ding
Jan 20, 2007·Biochemical Society Transactions·R Duncan
Nov 17, 2009·Biomacromolecules·Daniela DonghiRoberta Cavalli
Jan 22, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Lucia CalucciElisabetta Ranucci

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