Tailoring the physicochemical properties of core-crosslinked polymeric micelles for pharmaceutical applications

Affiliations

¹ Department of Biomaterials Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Cristal Therapeutics, Oxfordlaan 55, Maastricht 6229EV, The Netherlands.
² Cristal Therapeutics, Oxfordlaan 55, Maastricht 6229EV, The Netherlands.
³ Institute of Macromolecular Chemistry, the Czech Academy of Sciences, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic.
⁴ Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany.
⁵ Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen 52074, Germany.
⁶ Department of Biomaterials Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
⁷ Department of Biomaterials Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands.
⁸ Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands.
⁹ Department of Biomaterials Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen 52074, Germany; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands. Electronic address: tlammers@ukaachen.de.

PMID: 27401327
DOI: 10.1016/j.jconrel.2016.07.012

Tailoring the physicochemical properties of core-crosslinked polymeric micelles for pharmaceutical applications

Qizhi Hu et al. J Control Release. 2016.

. 2016 Dec 28;244(Pt B):314-325.

doi: 10.1016/j.jconrel.2016.07.012. Epub 2016 Jul 9.

Authors

Affiliations

¹ Department of Biomaterials Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Cristal Therapeutics, Oxfordlaan 55, Maastricht 6229EV, The Netherlands.
² Cristal Therapeutics, Oxfordlaan 55, Maastricht 6229EV, The Netherlands.
³ Institute of Macromolecular Chemistry, the Czech Academy of Sciences, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic.
⁴ Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany.
⁵ Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen 52074, Germany.
⁶ Department of Biomaterials Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
⁷ Department of Biomaterials Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands.
⁸ Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands.
⁹ Department of Biomaterials Science and Technology, Section: Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen 52074, Germany; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht 3584CG, The Netherlands. Electronic address: tlammers@ukaachen.de.

PMID: 27401327
DOI: 10.1016/j.jconrel.2016.07.012

Abstract

To optimally exploit the potential of (tumor-) targeted nanomedicines, platform technologies are needed in which physicochemical and pharmaceutical properties can be tailored according to specific medical needs and applications. We here systematically customized the properties of core-crosslinked polymeric micelles (CCPM). The micelles were based on mPEG-b-pHPMAmLac_n (i.e. methoxy poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate]), similar to the block copolymer composition employed in CriPec® docetaxel, which is currently in phase I clinical trials. The CCPM platform was tailored with regard to size (30 to 100nm), nanocarrier degradation (1month to 1year) and drug release kinetics (10 to 90% in 1week). This was achieved by modulating the molecular weight of the block copolymer, the type and density of the crosslinking agent, and the hydrolytic sensitivity of the drug linkage, respectively. The high flexibility of CCPM facilitates the development of nanomedicinal products for specific therapeutic applications.

Keywords: Core-crosslinking; Drug release; Drug targeting; Nanomedicine; Polymeric micelles.

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Tailoring the physicochemical properties of core-crosslinked polymeric micelles for pharmaceutical applications

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Tailoring the physicochemical properties of core-crosslinked polymeric micelles for pharmaceutical applications

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