Effect of Radical Polymerization Method on Pharmaceutical Properties of Π Electron-Stabilized HPMA-Based Polymeric Micelles

Armin Azadkhah Shalmani; Zaheer Ahmed; Maryam Sheybanifard; Alec Wang; Marek Weiler; Eva Miriam Buhl; Geir Klinkenberg; Ruth Schmid; Wim Hennink; Fabian Kiessling; Josbert M. Metselaar; Twan Lammers; Quim Peña; Yang Shi

doi:10.1021/acs.biomac.2c01261

Effect of Radical Polymerization Method on Pharmaceutical Properties of Π Electron-Stabilized HPMA-Based Polymeric Micelles

Armin Azadkhah Shalmani, Zaheer Ahmed, Maryam Sheybanifard, Alec Wang, Marek Weiler, Eva Miriam Buhl, Geir Klinkenberg, Ruth Schmid, Wim Hennink, Fabian Kiessling, Josbert M. Metselaar, Twan Lammers^*, Quim Peña^*, Yang Shi^*

^*Corresponding author for this work

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

Abstract

Polymeric micelles are among the most extensively used drug delivery systems. Key properties of micelles, such as size, size distribution, drug loading, and drug release kinetics, are crucial for proper therapeutic performance. Whether polymers from more controlled polymerization methods produce micelles with more favorable properties remains elusive. To address this question, we synthesized methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl)methacrylamide) (mPEG-b-p(HPMAm-Bz)) block copolymers of three different comparable molecular weights (∼9, 13, and 20 kDa), via both conventional free radical (FR) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were subsequently employed to prepare empty and paclitaxel-loaded micelles. While FR polymers had relatively high dispersities (Đ ∼ 1.5-1.7) compared to their RAFT counterparts (Đ ∼ 1.1-1.3), they formed micelles with similar pharmaceutical properties (e.g., size, size distribution, critical micelle concentration, cytotoxicity, and drug loading and retention). Our findings suggest that pharmaceutical properties of mPEG-b-p(HPMAm-Bz) micelles do not depend on the synthesis route of their constituent polymers.

Original language	English
Pages (from-to)	4444-4453
Number of pages	10
Journal	Biomacromolecules
Volume	24
Issue number	10
DOIs	https://doi.org/10.1021/acs.biomac.2c01261
Publication status	Published - 9 Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society

Funding

The authors are grateful for financial support by the German Research Foundation (DFG: SH1223/1-1; LA2937/4-1; GRK/RTG 2735 (project number 331065168)), the German Federal Ministry of Research and Education (BMBF: Gezielter Wirkstofftransport, PP-TNBC, Project No. 16GW0319K), Higher Education Commission of Pakistan and German Academic Exchange Services (HEC-DAAD Pakistan), and the European Research Council (ERC: Meta-Targeting (864121); BeaT-IT (101040996)).

Funders	Funder number
PP-TNBC	16GW0319K
European Research Council	101040996, 864121
Deutscher Akademischer Austauschdienst
the Deutsche Forschungsgemeinschaft	GRK/RTG 2735, LA2937/4-1, SH1223/1-1, 331065168
Bundesministerium für Bildung und Forschung
Higher Education Commision, Pakistan

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10.1021/acs.biomac.2c01261

shalmani-et-al-2023-effect-of-radical-polymerization-method-on-pharmaceutical-properties-of-π-electron-stabilized-hpmaFinal published version, 6.97 MBLicence: Taverne

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Shalmani, A. A., Ahmed, Z., Sheybanifard, M., Wang, A., Weiler, M., Buhl, E. M., Klinkenberg, G., Schmid, R., Hennink, W., Kiessling, F., Metselaar, J. M., Lammers, T., Peña, Q., & Shi, Y. (2023). Effect of Radical Polymerization Method on Pharmaceutical Properties of Π Electron-Stabilized HPMA-Based Polymeric Micelles. Biomacromolecules, 24(10), 4444-4453. https://doi.org/10.1021/acs.biomac.2c01261

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title = "Effect of Radical Polymerization Method on Pharmaceutical Properties of Π Electron-Stabilized HPMA-Based Polymeric Micelles",

abstract = "Polymeric micelles are among the most extensively used drug delivery systems. Key properties of micelles, such as size, size distribution, drug loading, and drug release kinetics, are crucial for proper therapeutic performance. Whether polymers from more controlled polymerization methods produce micelles with more favorable properties remains elusive. To address this question, we synthesized methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl)methacrylamide) (mPEG-b-p(HPMAm-Bz)) block copolymers of three different comparable molecular weights (∼9, 13, and 20 kDa), via both conventional free radical (FR) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were subsequently employed to prepare empty and paclitaxel-loaded micelles. While FR polymers had relatively high dispersities ({\D} ∼ 1.5-1.7) compared to their RAFT counterparts ({\D} ∼ 1.1-1.3), they formed micelles with similar pharmaceutical properties (e.g., size, size distribution, critical micelle concentration, cytotoxicity, and drug loading and retention). Our findings suggest that pharmaceutical properties of mPEG-b-p(HPMAm-Bz) micelles do not depend on the synthesis route of their constituent polymers.",

author = "Shalmani, {Armin Azadkhah} and Zaheer Ahmed and Maryam Sheybanifard and Alec Wang and Marek Weiler and Buhl, {Eva Miriam} and Geir Klinkenberg and Ruth Schmid and Wim Hennink and Fabian Kiessling and Metselaar, {Josbert M.} and Twan Lammers and Quim Pe{\~n}a and Yang Shi",

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month = oct,

day = "9",

doi = "10.1021/acs.biomac.2c01261",

language = "English",

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Shalmani, AA, Ahmed, Z, Sheybanifard, M, Wang, A, Weiler, M, Buhl, EM, Klinkenberg, G, Schmid, R, Hennink, W, Kiessling, F, Metselaar, JM, Lammers, T, Peña, Q & Shi, Y 2023, 'Effect of Radical Polymerization Method on Pharmaceutical Properties of Π Electron-Stabilized HPMA-Based Polymeric Micelles', Biomacromolecules, vol. 24, no. 10, pp. 4444-4453. https://doi.org/10.1021/acs.biomac.2c01261

TY - JOUR

T1 - Effect of Radical Polymerization Method on Pharmaceutical Properties of Π Electron-Stabilized HPMA-Based Polymeric Micelles

AU - Shalmani, Armin Azadkhah

AU - Ahmed, Zaheer

AU - Sheybanifard, Maryam

AU - Wang, Alec

AU - Weiler, Marek

AU - Buhl, Eva Miriam

AU - Klinkenberg, Geir

AU - Schmid, Ruth

AU - Hennink, Wim

AU - Kiessling, Fabian

AU - Metselaar, Josbert M.

AU - Lammers, Twan

AU - Peña, Quim

AU - Shi, Yang

PY - 2023/10/9

Y1 - 2023/10/9

N2 - Polymeric micelles are among the most extensively used drug delivery systems. Key properties of micelles, such as size, size distribution, drug loading, and drug release kinetics, are crucial for proper therapeutic performance. Whether polymers from more controlled polymerization methods produce micelles with more favorable properties remains elusive. To address this question, we synthesized methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl)methacrylamide) (mPEG-b-p(HPMAm-Bz)) block copolymers of three different comparable molecular weights (∼9, 13, and 20 kDa), via both conventional free radical (FR) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were subsequently employed to prepare empty and paclitaxel-loaded micelles. While FR polymers had relatively high dispersities (Đ ∼ 1.5-1.7) compared to their RAFT counterparts (Đ ∼ 1.1-1.3), they formed micelles with similar pharmaceutical properties (e.g., size, size distribution, critical micelle concentration, cytotoxicity, and drug loading and retention). Our findings suggest that pharmaceutical properties of mPEG-b-p(HPMAm-Bz) micelles do not depend on the synthesis route of their constituent polymers.

AB - Polymeric micelles are among the most extensively used drug delivery systems. Key properties of micelles, such as size, size distribution, drug loading, and drug release kinetics, are crucial for proper therapeutic performance. Whether polymers from more controlled polymerization methods produce micelles with more favorable properties remains elusive. To address this question, we synthesized methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl)methacrylamide) (mPEG-b-p(HPMAm-Bz)) block copolymers of three different comparable molecular weights (∼9, 13, and 20 kDa), via both conventional free radical (FR) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were subsequently employed to prepare empty and paclitaxel-loaded micelles. While FR polymers had relatively high dispersities (Đ ∼ 1.5-1.7) compared to their RAFT counterparts (Đ ∼ 1.1-1.3), they formed micelles with similar pharmaceutical properties (e.g., size, size distribution, critical micelle concentration, cytotoxicity, and drug loading and retention). Our findings suggest that pharmaceutical properties of mPEG-b-p(HPMAm-Bz) micelles do not depend on the synthesis route of their constituent polymers.

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DO - 10.1021/acs.biomac.2c01261

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SN - 1525-7797

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IS - 10

ER -

Effect of Radical Polymerization Method on Pharmaceutical Properties of Π Electron-Stabilized HPMA-Based Polymeric Micelles

Abstract

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Funding

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