pH-Sensitive drug-conjugates on water-soluble polymer frameworks

Abu Bakkar Siddique, Youngjun Cho, Yujin Kim, Sung Hoon Bahng, Sung Woo Kim, Jae Yeol Lee, Ho Jung Kang, Sehoon Kim, You Han Bae, Jungahn Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A potent synthetic methodology is introduced to generate a useful intermediate for the preparation of 'smart' polymeric pro-drugs. Herein, living anionic block polymerization of ethylene oxide (EO) and N-phenylmaleimide (N-PMI), as well as the Gabriel process, are introduced. Hydrazinolysis of the resulting poly(ethylene oxide)-block-poly(N-PMI) (PEO-b-PN-PMI) using hydrazine under acidic conditions leads to the production of PEO-based frameworks with hydrazide (HZ) groups. The HZ groups are found to effect the formation of an acid-sensitive bond in reactions with medicines or drugs under neutral conditions (pH 7.2). The PEO-HZ intermediate, which shows a strong triplet splitting patterned chemical shift in the range Δ = 6.5-8.5 ppm, represents the most powerful material employed for mass production of smart polymeric pro-drugs while controlling the drug-loading yield. Water-soluble "smart" polymeric pro-drugs, such as poly(ethylene oxide)-doxorubicin (PEO-HZ-Dox), poly(ethylene oxide)-methotrexate (PEO-HZ-MTX), and poly(ethylene oxide)-folate (PEO-HZ-FA) conjugates, show excellent acid-sensitive release profiles in water or alcohol at pH 4.5.

Original languageEnglish
Pages (from-to)265-276
Number of pages12
JournalMacromolecular Chemistry and Physics
Volume216
Issue number3
DOIs
Publication statusPublished - 2015 Feb 1
Externally publishedYes

Keywords

  • Acid-dependent drug-release
  • Living anionic block copolymerization
  • PEO-drug conjugates
  • Poly(ethylene oxide)-based block copolymers

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Physical and Theoretical Chemistry
  • Polymers and Plastics
  • Organic Chemistry
  • Materials Chemistry

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  • Cite this

    Siddique, A. B., Cho, Y., Kim, Y., Bahng, S. H., Kim, S. W., Lee, J. Y., Kang, H. J., Kim, S., Bae, Y. H., & Kim, J. (2015). pH-Sensitive drug-conjugates on water-soluble polymer frameworks. Macromolecular Chemistry and Physics, 216(3), 265-276. https://doi.org/10.1002/macp.201400457