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Issue 7, 2015

Well-defined diblock brush polymer–drug conjugates for sustained delivery of paclitaxel

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Abstract

Using the 3rd generation Grubbs’ catalyst as the initiator, diblock brush polymer drug conjugates (BPDCs) were synthesized by sequential ring-opening metathesis polymerization (ROMP) of a hydrophilic poly(ethylene glycol) (PEG)-based norbornene (NB)-functionalized macromonomer and a hydrophobic paclitaxel (PTXL)-based NB-functionalized monomer. These amphiphilic diblock BPDCs had well-defined structures, with narrow molecular weight distributions (Mw/Mn = 1.10–1.16). They self-assembled into multi-molecular nanostructures in aqueous solutions. Although the PTXL moieties were connected to the backbone with cycloacetal-based conjugation linkages, the cleavage of these linkages from the assemblies of diblock BPDCs was relatively slow and exhibited limited acid-sensitivity, indicating a significant influence of the macromolecular structure and assembly of BPDCs on their drug release behaviour. The cytotoxicity study not only showed that the diblock BPDCs are therapeutically effective against cancer cells, but also revealed a correlation between cytotoxicity and grafting structures of BPDCs. In summary, the results obtained in this work provide new insight into the structure-dependent properties of brush polymer-based drug delivery systems.

Graphical abstract: Well-defined diblock brush polymer–drug conjugates for sustained delivery of paclitaxel

Supplementary files

Article information


Submitted
29 Dec 2014
Accepted
29 Jan 2015
First published
11 Feb 2015

Biomater. Sci., 2015,3, 1078-1084
Article type
Paper
Author version available

Well-defined diblock brush polymer–drug conjugates for sustained delivery of paclitaxel

J. Zou, Y. Yu, Y. Li, W. Ji, C. Chen, W. Law, P. N. Prasad and C. Cheng, Biomater. Sci., 2015, 3, 1078 DOI: 10.1039/C4BM00458B

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