Focus Article
Applications of polymer micelles for imaging and drug delivery Sara Movassaghian,1,2 Olivia M. Merkel1,2 and Vladimir P. Torchilin3∗ Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers, are widely considered as convenient nano-carriers for a variety of applications, such as diagnostic imaging, and drug and gene delivery. They have demonstrated a variety of favorable properties including biocompatibility, longevity, high stability in vitro and in vivo, capacity to effectively solubilize a variety of poorly soluble drugs, changing the release profile of the incorporated pharmaceutical agents, and the ability to accumulate in the target zone based on the enhanced permeability and retention effect. Moreover, additional functions can be imparted to the micelle-based delivery systems by engineering their surface for specific applications. Various targeting ligands can be attached for cell or intracellular accumulation at a site of interest. Also, the chelation or incorporation of imaging moieties into the micelle structure enables in vivo biodistribution studies. Moreover, pH-, thermo-, ultrasound-, enzyme- and light-sensitive block-copolymers allow for controlled micelle dissociation and triggered drug release in response to the pathological environment-specific stimuli and/or externally applied signals. The combination of these approaches can further improve specificity and efficacy of micelle-based drug delivery to promote the development of smart multifunctional micelles. © 2015 Wiley Periodicals, Inc. How to cite this article:
WIREs Nanomed Nanobiotechnol 2015. doi: 10.1002/wnan.1332
INTRODUCTION
I
n the emerging field of pharmaceutical nanotechnology, nanoparticles hold promise to overcome challenges related to unsatisfactory therapeutic responses of so-called old drugs and major formulation-related performance issues of newly introduced chemical compounds. Among the different forms of nanoparticles, polymeric micelles have received growing scientific attention. Since their first application as nanocarriers in drug delivery system in the 1980s,1 extensive studies ∗ Correspondence
to: [email protected]
1 Department
of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA 2 Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA 3 Center
for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA Conflict of interest: The authors have declared no conflicts of interest for this article.
have shed light on the properties of micelles and introduced them as a promising platform for multiple pharmaceutical applications.2 They have been evaluated for therapeutic agent (drug, gene, and protein) delivery systems, as well as for diagnostic application. Almost all drug administration routes (parenteral, oral, nasal, and ocular) have benefited from micellar forms of drugs in terms of either increased bioavailability or reduction of adverse effects.3–6 This class of drug carriers offers a clear set of advantages7 including (1) the nano-size range (typically
Applications of polymer micelles for imaging and drug delivery Sara Movassaghian,1,2 Olivia M. Merkel1,2 and Vladimir P. Torchilin3∗ Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers, are widely considered as convenient nano-carriers for a variety of applications, such as diagnostic imaging, and drug and gene delivery. They have demonstrated a variety of favorable properties including biocompatibility, longevity, high stability in vitro and in vivo, capacity to effectively solubilize a variety of poorly soluble drugs, changing the release profile of the incorporated pharmaceutical agents, and the ability to accumulate in the target zone based on the enhanced permeability and retention effect. Moreover, additional functions can be imparted to the micelle-based delivery systems by engineering their surface for specific applications. Various targeting ligands can be attached for cell or intracellular accumulation at a site of interest. Also, the chelation or incorporation of imaging moieties into the micelle structure enables in vivo biodistribution studies. Moreover, pH-, thermo-, ultrasound-, enzyme- and light-sensitive block-copolymers allow for controlled micelle dissociation and triggered drug release in response to the pathological environment-specific stimuli and/or externally applied signals. The combination of these approaches can further improve specificity and efficacy of micelle-based drug delivery to promote the development of smart multifunctional micelles. © 2015 Wiley Periodicals, Inc. How to cite this article:
WIREs Nanomed Nanobiotechnol 2015. doi: 10.1002/wnan.1332
INTRODUCTION
I
n the emerging field of pharmaceutical nanotechnology, nanoparticles hold promise to overcome challenges related to unsatisfactory therapeutic responses of so-called old drugs and major formulation-related performance issues of newly introduced chemical compounds. Among the different forms of nanoparticles, polymeric micelles have received growing scientific attention. Since their first application as nanocarriers in drug delivery system in the 1980s,1 extensive studies ∗ Correspondence
to: [email protected]
1 Department
of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA 2 Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA 3 Center
for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA Conflict of interest: The authors have declared no conflicts of interest for this article.
have shed light on the properties of micelles and introduced them as a promising platform for multiple pharmaceutical applications.2 They have been evaluated for therapeutic agent (drug, gene, and protein) delivery systems, as well as for diagnostic application. Almost all drug administration routes (parenteral, oral, nasal, and ocular) have benefited from micellar forms of drugs in terms of either increased bioavailability or reduction of adverse effects.3–6 This class of drug carriers offers a clear set of advantages7 including (1) the nano-size range (typically
