Characterising the size and shape of polyamidoamines in solution as a function of pH using neutron scattering and pulsed-gradient spin-echo NMR

International Journal of Pharmaceutics
Zeena KhayatRuth Duncan

Abstract

Bioresponsive polymers are being developed as synthetic viral mimetics to enhance the intracellular delivery of macromolecular therapeutic agents such as genes, proteins and peptides. In this context we have designed pH-responsive, amphoteric polyamidoamines (PAAs) which change conformation on passing from a neutral pH (extracellular) to an acidic pH (endosomal and lysosomal) environments. PAAs have already demonstrated cytosolic delivery of genes and non-permeant toxins (e.g. gelonin and ricin A chain). The aim of this study was to use small-angle neutron scattering (SANS) to investigate the most likely shape of the hydrochloride salt form of one particular PAA (ISA23) in solution, under pH conditions that mimic those the polymer would be expected to encounter during endocytic internalisation (pH 7.4-3). It was shown that models based on a Gaussian coil representation of the polymer conformation described the SANS data better over this pH range than models based on a rod-like conformation. The conformation of ISA23 at 37 degrees C was expanded (radius of gyration approximately 80A) at pH approximately 3 but collapsed with an increase in pH (radius of gyration approximately 20A at pH 7.4), a conclusion also reached in a model-f...Continue Reading

Citations

May 22, 2008·Expert Opinion on Drug Delivery·María J VicentAntonio Pineda-Lucena
Feb 15, 2011·Expert Opinion on Drug Delivery·Paul D R Dyer, Simon C W Richardson
Feb 1, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Grégory Coué, Johan F J Engbersen
Oct 14, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Simon C W RichardsonRuth Duncan
Jul 28, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Martin Piest, Johan F J Engbersen
Jul 25, 2013·Advanced Drug Delivery Reviews·Arun K IyerMansoor M Amiji
Jan 27, 2012·Macromolecular Bioscience·Rajeswari RavichandranSeeram Ramakrishna
Nov 20, 2008·Macromolecular Bioscience·Nathalie LavignacRuth Duncan
Jan 22, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Lucia CalucciElisabetta Ranucci
Oct 7, 2011·Molecular Pharmaceutics·Ruth Duncan, Rogerio Gaspar
Dec 7, 2013·The Journal of Physical Chemistry. B·Faheem N PadiaJian R Lu

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