Poly(ethylene glycol)-b-poly(lysine) copolymer bearing nitroaromatics for hypoxia-sensitive drug delivery

Acta Biomater. 2016 Jan:29:261-270. doi: 10.1016/j.actbio.2015.10.011. Epub 2015 Oct 22.

Abstract

Hypoxia occurs in a variety of pathological conditions including stroke, rheumatoid arthritis, atherosclerosis, and tumors. In this study, an amphiphilic block copolymer, composed of poly(ethylene glycol) as the hydrophilic block and poly(ε-(4-nitro)benzyloxycarbonyl-L-lysine) as the hydrophobic block, was prepared for hypoxia-sensitive drug delivery. Owing to its amphiphilic nature, the block copolymer formed micelles and encapsulated doxorubicin (DOX) in an aqueous condition. The DOX-loaded micelles exhibited rapid intracellular release of DOX under the hypoxic condition, implying high potential as a drug carrier for cancer therapy.

Statement of significance: Hypoxia occurs in a variety of pathological conditions including stroke, rheumatoid arthritis, atherosclerosis, and tumors. In this study, we developed a novel type of hypoxia-sensitive polymeric micelles (HS-PMs) that can specifically release the drug under the hypoxic conditions. HS-PMs were prepared using poly(ethylene glycol) as the hydrophilic block and poly(ε-(4-nitro)benzyloxycarbonyl-L-lysine) as the hydrophobic block. Owing to its amphiphilic nature, the block copolymer formed micelles and encapsulated doxorubicin (DOX) in an aqueous condition. The DOX-loaded micelles exhibited rapid intracellular release of DOX under the hypoxic condition. Overall, it is evident that the HS-PMs prepared in this study have the potential to effectively deliver hydrophobic drugs into the hypoxic cells involved in various intractable diseases.

Keywords: Block copolymer; Cancer; DOX; Drug delivery; Hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Hypoxia
  • Cell Line, Tumor
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Humans
  • Nitrobenzenes* / chemistry
  • Nitrobenzenes* / pharmacokinetics
  • Nitrobenzenes* / pharmacology
  • Polyethylene Glycols* / chemistry
  • Polyethylene Glycols* / pharmacokinetics
  • Polyethylene Glycols* / pharmacology
  • Polylysine* / chemistry
  • Polylysine* / pharmacokinetics
  • Polylysine* / pharmacology

Substances

  • Delayed-Action Preparations
  • Nitrobenzenes
  • Polylysine
  • Polyethylene Glycols
  • Doxorubicin
  • polyethylene glycol 1000