Issue 1, 2019

Synthesis of a SN38 prodrug grafted to amphiphilic phosphorylcholine polymers and their prodrug miceller properties

Abstract

Polymer prodrug micelles, combining the advantages of prodrugs and polymer micelles, can greatly improve the solubility, permeability and stability of drugs. In this work, amphiphilic block copolymers poly(α-azide caprolactone-co-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine), P(ACL-co-CL)-b-PMPC, were synthesized, and an antineoplastic drug 7-ethyl-10-hydroxy camptothecin (SN38) was grafted to the amphiphilic copolymers to obtain a prodrug and their micelles. The preparation of P(ACL-co-CL)-b-PMPC was proceeded by ring-opening polymerization of ε-caprolactone/α-bromide caprolactone, converting the bromide to an azide, and atom transfer radical polymerization (ATRP). The camptothecin derivative SN38-alkyne was bonded to the polymer to obtain P(CL/CL-g-SN38)-b-PMPC by a “click reaction”. The obtained polymer–drug complex can easily self-assemble to form prodrug micelles with the shell composed of PMPC and the core composed of PCL and SN38. The micelles presented characteristics including improved drug loading efficiency and stabilization of the drug. In vivo, the retention time of the prodrug micelles in blood could be tripled, and the clearance was delayed compared with the SN38 solution. The in vivo anti-tumor experiments demonstrated that the prodrug micelles had a better treatment effect and low toxicity to 4T1-bearing BALB/C mice.

Graphical abstract: Synthesis of a SN38 prodrug grafted to amphiphilic phosphorylcholine polymers and their prodrug miceller properties

Supplementary files

Article information

Article type
Paper
Submitted
27 Sep 2018
Accepted
11 Nov 2018
First published
17 Nov 2018

New J. Chem., 2019,43, 481-491

Synthesis of a SN38 prodrug grafted to amphiphilic phosphorylcholine polymers and their prodrug miceller properties

F. Chen, Y. Cai, L. Huang, Y. Chen and X. Luo, New J. Chem., 2019, 43, 481 DOI: 10.1039/C8NJ04908D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements