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Single Polymer-drug Conjugate Carrying Two Drugs for Fixed-dose Codelivery

Abstract

Yan Li, Haiqing Dong, Xuequan Li, Donglu Shi and Yongyong Li

Fixed-dose combination chemotherapy holds great potential for management of cancer. Thus a drug delivery system which can administer a controlled ratio of several drugs simultaneously and control the drug release at the cancer site is highly desired. In this work, a fixed-dose dual drug loaded polymer micelle is formed by the self-assembly of a single polymer–drug conjugate carrying a combination of drugs. A predetermined ratio of the two drugs can be obtained via a facile and efficient solid-phase synthesis method. MTT assay demonstrated that the polymer micelles are more effective in altering the proliferation rate of MCF-7 tumor cells due to its higher solubility than free drugs. Furthermore, the introduction of the redox-sensitive disulfide linker between the hydrophilic PEG and the hydrophobic drugs facilitates drug release in tumor cellular redox environment and thus enhances the therapeutic effectiveness dramatically.

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