Elsevier

Journal of Controlled Release

Volume 130, Issue 2, 10 September 2008, Pages 98-106
Journal of Controlled Release

Review
Pluronic block copolymers: Evolution of drug delivery concept from inert nanocarriers to biological response modifiers

https://doi.org/10.1016/j.jconrel.2008.04.013Get rights and content

Abstract

Polymer nanomaterials have sparked a considerable interest as vehicles used for diagnostic and therapeutic agents; research in nanomedicine has not only become a frontier movement but is also a revolutionizing drug delivery field. A common approach for building a drug delivery system is to incorporate the drug within the nanocarrier that results in increased solubility, metabolic stability, and improved circulation time. With this foundation, nanoparticles with stealth properties that can circumvent RES and other clearance and defense mechanisms are the most promising. However, recent developments indicate that select polymer nanomaterials can implement more than only inert carrier functions by being biological response modifiers. One representative of such materials is Pluronic block copolymers that cause various functional alterations in cells. The key attribute for the biological activity of Pluronics is their ability to incorporate into membranes followed by subsequent translocation into the cells and affecting various cellular functions, such as mitochondrial respiration, ATP synthesis, activity of drug efflux transporters, apoptotic signal transduction, and gene expression. As a result, Pluronics cause drastic sensitization of MDR tumors to various anticancer agents, enhance drug transport across the blood brain and intestinal barriers, and causes transcriptional activation of gene expression both in vitro and in vivo. Collectively, these studies suggest that Pluronics have a broad spectrum of biological response modifying activities which make it one of the most potent drug targeting systems available, resulting in a remarkable impact on the emergent field of nanomedicine.

Section snippets

Pluronic unimers and micelles

Polymer-based nanotechnology became one of the most attractive and fast growing areas of pharmaceutical research. The materials that are currently being researched include polymer micelles, polymer-DNA complexes (“polyplexes”), nanogels, liposomes, and other nanoscale sized materials for medical use that are collectively called nanomedicines. Specific arrangements of polymeric molecules at the nanoscale achieved within such materials represent unique opportunities for safe and efficient

Biological activity of pluronic molecules

The polymers used for drug delivery were considered as biologically inert components that protect drugs from degradation, prolong exposure of drugs to tissues, and enhance transport of drugs into cells. However, this paradigm is undergoing substantial evolution due to growing evidence that select synthetic polymers can drastically alter specific cellular responses [42], [43], [44]. Thus, besides their ability to self-assemble into micelles, Pluronic block copolymers were shown to be potent

Acknowledgments

This study has been supported by a National Institutes of Health grants CA89225, CA116591, NS36229, NS051335 awarded to AVK. We acknowledge the graduate students in the UNMC Pharmaceutical Sciences Graduate Program, Daria Alakhova, Zagit Gaimalov, Gaurav Sahay and Amit Sharma, as well as Dr. Zhihui Yang for their scientific contributions in a number of recent studies in press or in preparation.

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