Polymersomes: A new multi-functional tool for cancer diagnosis and therapy
Section snippets
Background
Nanosized carriers are prime candidates for the delivery of highly toxic and/or hydrophobic therapeutic agents. These delivery vehicles have the potential to augment the pharmacodynamic and pharmacokinetic profiles of drug molecules, thereby enhancing the therapeutic efficacy of the pharmaceutical agents [1]. Further, encapsulating the drug molecule in a delivery system can increase in vivo stability, extend its blood circulation time, and further provide a means for controlling the release of
Diblock copolymers forming vesicles and release mechanisms
In this section, we highlight some of the polymer formulations, which have led to the formation of polymersomes, that have demonstrated promise for controlled release of pharmaceuticals.
Initial polymersome research by Hammer and Discher used poly(ethylene oxide)-block-poly(ethylethylene) (PEO-b-PEE) diblock copolymers to demonstrate the formation of polymersomes in aqueous solution, as well as to characterize the vesicles material and physical properties [3]. Additional work in the field has
Therapeutic applications of polymersomes
Currently, many compounds with toxic side effects and/or low bioavailability hold extraordinary promise as potential therapeutic agents. However, limited bioavailability of hydrophobic compounds and/or toxic side effects of these molecules can render their therapeutic value ineffective. Further, the ability of the therapeutic agents to reach the target site can be limited by the body’s clearance. Thus, the development of a polymeric delivery vehicle with specifically tuned pharmacokinetics,
Diagnostic applications of polymersomes
The ability to non-invasively image nanoparticles in vivo is a major advantage in determining their biodistribution and developing these delivery vehicles for both therapeutic and diagnostic applications. Biodistribution studies with polymersomes, in particular, would be greatly aided by the encapsulation of an imaging agent in the vesicles; this would enable non-invasive monitoring of the location of vesicles during drug delivery without the need to sacrifice the animal. Although nanoparticles
Polymersome surface modifications for delivery and therapy
Biologically-active molecules conjugated to the surfaces of polymersomes can be used to direct these nanoparticles to sites of disease and inflammation. Modifying polymer vesicles with biological ligands enables targeting of upregulated receptors and molecules on affected cells in vitro and in vivo, thereby enhancing the nanoparticles’ EPR effect and further mitigating the potential toxic side effects of systemic delivery. Additionally, chemotherapeutics, when used in conjunction with molecular
Future directions
Polymersomes are new and valuable tools for both disease diagnosis and therapy. Our view is that the enhanced stability and tunability of polymersomes will ultimately lead to the development of effective carriers for in vivo drug delivery, molecular imaging, and cellular mimicry that extend well beyond what has thus far been achieved with phospholipid vesicles.
In drug delivery, the potential to co-encapsulate two drug molecules in the same polymersome enables combination therapies and
Acknowledgments
This work is funded, in part, under a grant through the Health Research Formula Funds, Commonwealth of Pennsylvania to R.M., M.J.T. and D.A.H. The Department specifically disclaims responsibility for any analyses, interpretations, or conclusions. This work is also supported, in part, under grants from the National Institutes of Health (EB003457-01 and CA115229-01A1) to D.A.H. and M.J.T. The authors thank N.A. Christian, and G. Robbins for sharing unpublished results and/or recently submitted
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