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 language | English |
|---|---|
| Pages (from-to) | 265-276 |
| Number of pages | 12 |
| Journal | Macromolecular Chemistry and Physics |
| Volume | 216 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2015 Feb 1 |
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