Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Evaluation of hyaluronic acid-protein conjugates for polymer masked-unmasked protein therapy

Ferguson, Elaine Lesley, Alshame, Alshame Mohamed J. and Thomas, David William 2010. Evaluation of hyaluronic acid-protein conjugates for polymer masked-unmasked protein therapy. International Journal of Pharmaceutics 402 (1-2) , pp. 95-102. 10.1016/j.ijpharm.2010.09.029

Full text not available from this repository.

Abstract

Bioresponsive polymers may effectively be utilized to enhance the circulation time and stability of biologically active proteins and peptides, while reducing their immunogenicity and toxicity. Recently, dextrin-epidermal growth factor (EGF) conjugates, which make use of the Polymer-masked UnMasked Protein Therapy (PUMPT) concept, have been developed and shown potential as modulators of impaired wound healing. This study investigated the potential of PUMPT using hyaluronic acid (HA) conjugates to mask activity and enhance protein stability, while allowing restoration of biological activity following triggered degradation. HA fragments (Mw similar to 90,000 g/mol), obtained by acid hydrolysis of Rooster comb HA, were conjugated to trypsin as a model enzyme or to EGF as a model growth factor. Conjugates contained 2.45 and 0.98% (w/w) trypsin or EGF, respectively, and contained <5% free protein. HA conjugation did not significantly alter trypsin's activity. However, incubation of the conjugate with physiological concentrations of HAase increased its activity to similar to 145% (p < 0.001) that of the free enzyme. In contrast, when HA-EGF conjugates were tested in vitro, no effect on cell proliferation was seen, even in the presence of HAase. HA conjugates did not display typical masking/unmasking behavior, HA-trypsin conjugates exhibited similar to 52% greater stability in the presence of elastase, compared to free trypsin, demonstrating the potential of HA conjugates for further development as modulators of tissue repair. (C) 2010 Elsevier B.V. All rights reserved.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QP Physiology
R Medicine > RK Dentistry
Uncontrolled Keywords: Polymer therapeutics; Hyaluronic acid; Bioresponsive; Nanomedicines; PUMPT
Publisher: Elsevier
ISSN: 0378-5173
Last Modified: 04 Feb 2019 22:31
URI: http://orca.cf.ac.uk/id/eprint/15848

Citation Data

Cited 13 times in Google Scholar. View in Google Scholar

Cited 31 times in Scopus. View in Scopus. Powered By Scopus® Data

Cited 16 times in Web of Science. View in Web of Science.

Actions (repository staff only)

Edit Item Edit Item