Non-cytotoxic polymer vesicles for rapid and efficient intracellular delivery

Faraday Discuss. 2008;139:143-59; discussion 213-28, 419-20. doi: 10.1039/b717431d.

Abstract

We have recently achieved efficient cytosolic delivery by using pH-sensitive poly(2-(methacryloyloxy)ethylphosphorylcholine)-co-poly(2-(diisopropylamino)ethylmethacrylate) (PMPC-PDPA) diblock copolymers that self-assemble to form vesicles, known as polymersomes, in aqueous solution. It is particularly noteworthy that these diblock copolymers form stable polymersomes at physiological pH but rapidly dissociate below pH 6 to give molecularly-dissolved copolymer chains (unimers). These PMPC-PDPA polymersomes are used to encapsulate nucleic acids for efficient intracellular delivery. Confocal laser scanning microscopy and fluorescence flow cytometry are used to quantify cellular uptake and to study the kinetics of this process. Finally, we examine how PMPC-PDPA polymersomes affect the viability of primary human cells (human dermal fibroblasts (HDF)), paying particular regard to whether inflammatory responses are triggered.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • DNA / administration & dosage*
  • Drug Delivery Systems*
  • Humans
  • Hydrogen-Ion Concentration
  • Methacrylates / administration & dosage*
  • Methacrylates / chemistry
  • Methacrylates / pharmacology
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / chemistry
  • Phosphorylcholine / pharmacology
  • Polymethacrylic Acids / administration & dosage*
  • Polymethacrylic Acids / chemistry
  • Polymethacrylic Acids / pharmacology

Substances

  • Methacrylates
  • Polymethacrylic Acids
  • poly(2-(diisopropylamino)ethyl methacrylate)
  • poly(2-methacryloyloxyethyl-phosphorylcholine)
  • Phosphorylcholine
  • DNA