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Impact of polymer tacticity on the physico-chemical behaviour of polymers proposed as therapeutics

Izzo, Lorella, Griffiths, Peter Charles, Nilmini, Renuka, King, Stephen M., Wallom, Kerri-Lee, Ferguson, Elaine Lesley and Duncan, Ruth 2011. Impact of polymer tacticity on the physico-chemical behaviour of polymers proposed as therapeutics. International Journal of Pharmaceutics 408 (1-2) , pp. 213-222. 10.1016/j.ijpharm.2011.02.003

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Abstract

Although water-soluble polymers are finding increasing use as polymer therapeutics, there has been little consideration of the effect of polymer stereochemistry on their physico-chemical and biological properties. The aim of this study was to investigate these properties using polymethacrylic acids (PMAs) of similar molecular weights with a difference in syndiotacticity of about 20% of rr triad content. Experiments to characterize the solution behaviour were conducted at pHs encountered during the transport, endocytic uptake and intracellular trafficking (7.4–3.0). These showed that with increasing rr triads, the polymer become less hydrophobic, a stronger acid, displayed a locally ordered solution conformation at pH 5.5, and interacted more strongly with dodecyl trimethylammonium bromide (DTAB) micelles. Preliminary cytotoxicity experiments using B16F10 melanoma cells showed lower toxicity in the concentration range of 1–100 μg/mL with increased rr triads. These observations indicate that the higher content of rr triads could drive a chain organization that minimize the influence of negative charges and so underline the importance of further, systematic studies to investigate the effect of tacticity on the behaviour of polymers in respect of their pharmacokinetics, toxicity and efficacy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Dentistry
Subjects: Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Polymer stereochemistry; Polymer conformation; Polymer therapeutics; Poly(methacrylic acid)
Publisher: Elsevier
ISSN: 0378-5173
Last Modified: 03 Apr 2018 20:36
URI: http://orca.cf.ac.uk/id/eprint/9743

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