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

Qizhi Hu; Cristianne Rijcken; Ethlinn van Gaal; Paul Brundel; Hana Kostkova; Tomas Etrych; Benjamin Weber; Matthias Barz; Fabian Kiessling; Jai Prakash; G Storm; Wim E. Hennink; Twan Lammers

doi:10.1016/j.jconrel.2016.07.012

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

Qizhi Hu, Cristianne Rijcken, Ethlinn van Gaal, Paul Brundel, Hana Kostkova, Tomas Etrych, Benjamin Weber, Matthias Barz, Fabian Kiessling, Jai Prakash, G Storm, Wim E. Hennink, Twan Lammers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 100 nm), nanocarrier degradation (1 month to 1 year) and drug release kinetics (10 to 90% in 1 week). 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.

Original language	English
Pages (from-to)	314-325
Number of pages	12
Journal	Journal of Controlled Release
Volume	244
DOIs	https://doi.org/10.1016/j.jconrel.2016.07.012
Publication status	Published - 28 Dec 2016

Keywords

Core-crosslinking
Drug release
Drug targeting
Nanomedicine
Polymeric micelles

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10.1016/j.jconrel.2016.07.012

TailoringFinal published version, 1.28 MBLicence: Taverne

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Hu, Q., Rijcken, C., van Gaal, E., Brundel, P., Kostkova, H., Etrych, T., Weber, B., Barz, M., Kiessling, F., Prakash, J., Storm, G., Hennink, W. E., & Lammers, T. (2016). Tailoring the physicochemical properties of core-crosslinked polymeric micelles for pharmaceutical applications. Journal of Controlled Release, 244, 314-325. https://doi.org/10.1016/j.jconrel.2016.07.012

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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-pHPMAmLacn (i.e. methoxy poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate]), similar to the block copolymer composition employed in CriPec{\textregistered} docetaxel, which is currently in phase I clinical trials. The CCPM platform was tailored with regard to size (30 to 100 nm), nanocarrier degradation (1 month to 1 year) and drug release kinetics (10 to 90% in 1 week). 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",

author = "Qizhi Hu and Cristianne Rijcken and {van Gaal}, Ethlinn and Paul Brundel and Hana Kostkova and Tomas Etrych and Benjamin Weber and Matthias Barz and Fabian Kiessling and Jai Prakash and G Storm and Hennink, {Wim E.} and Twan Lammers",

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doi = "10.1016/j.jconrel.2016.07.012",

language = "English",

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journal = "Journal of Controlled Release",

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AU - Hu, Qizhi

AU - Rijcken, Cristianne

AU - van Gaal, Ethlinn

AU - Brundel, Paul

AU - Kostkova, Hana

AU - Etrych, Tomas

AU - Weber, Benjamin

AU - Barz, Matthias

AU - Kiessling, Fabian

AU - Prakash, Jai

AU - Storm, G

AU - Hennink, Wim E.

AU - Lammers, Twan

PY - 2016/12/28

Y1 - 2016/12/28

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AB - 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-pHPMAmLacn (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 100 nm), nanocarrier degradation (1 month to 1 year) and drug release kinetics (10 to 90% in 1 week). 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.

KW - Core-crosslinking

KW - Drug release

KW - Drug targeting

KW - Nanomedicine

KW - Polymeric micelles

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ER -

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

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Keywords

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