Biomembrane-Active Molecular Switches as Tools for Intracellular Drug Delivery
Volga Bulmus AA Center for Advanced Macromolecular Design (CAMD), School of Chemical Engineering and Industrial Chemistry, University of New South Wales, Sydney NSW 2052, Australia. Email: vbulmus@unsw.edu.au
Volga Bulmus received her Ph.D. in bioengineering from Hacettepe University, Ankara, in 2000. She worked as a postdoctoral fellow with Allan Hoffman and Pat Stayton at the University of Washington on the development of pH-responsive polymers for intracellular delivery of biomolecular drugs. In January 2004 she joined the CAMD at the University of New South Wales. Her research interests include the design, synthesis, and evaluation of polymeric materials for targetted drug delivery systems and diagnostics. |
Australian Journal of Chemistry 58(6) 411-422 https://doi.org/10.1071/CH05066
Submitted: 9 March 2005 Accepted: 21 April 2005 Published: 14 June 2005
Abstract
Many therapeutic strategies, such as gene therapy and vaccine development require the delivery of polar macromolecules (e.g. DNA, RNA, and proteins) to intracellular sites at a therapeutic concentration. For such macromolecular therapeutics, cellular membranes constitute a major transport barrier that must be overcome before these drugs can exert their biological activity inside cells. A number of biological organisms, e.g. viruses and toxins, efficiently destabilize the cellular membranes upon a trigger, such as low pH, and facilitate the delivery of their biological cargo to the cytoplasm of host cell. pH-responsive synthetic peptides and polymers have been designed to mimic the function of membrane-destabilizing natural organisms and evaluated as a part of drug delivery systems. In this Review, pH-dependent membrane activity of natural and synthetic systems is reviewed, focussing on fundamental and practical aspects of pH-responsive, membrane-disruptive synthetic polymers in intracellular drug delivery.
The author gratefully acknowledges the University of New South Wales (UNSW) Vice Chancellor’s/NewSouth Global Research Fellowship. The author would also like to thank Dr Charles Y. Cheung (University of Colorado) for review of the manuscript.
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