Feedback-regulated paclitaxel delivery based on poly(N,N-dimethylaminoethyl methacrylate-co-2-hydroxyethyl methacrylate) nanoparticles

Biomaterials. 2008 Apr;29(12):1950-7. doi: 10.1016/j.biomaterials.2007.12.041. Epub 2008 Feb 5.

Abstract

pH-Sensitive poly(N,N-dimethylaminoethyl methacrylate (DMAEMA)/2-hydroxyethyl methacrylate (HEMA)) nanoparticles were prepared for the triggered release of paclitaxel within a tumor microenvironment. Tumors exhibit a lower extracellular pH than normal tissues. We show that paclitaxel release from DMAEMA/HEMA particles can be actively triggered by small, physiological changes in pH (within 0.2-0.6 pH units). Monodispersed nanoparticles were synthesized by forming an O/W emulsion followed by photopolymerization. Particles were characterized by transmission electron microscopy, dynamic light scattering, electrophoresis, and cytotoxicity. High release rates and swelling ratios are achieved at low pH, low crosslinking density, and high content of DMAEMA. Paclitaxel release is limited to 9% of the payload at pH 7.4 after a 2-h incubation at 37 degrees C. After adjusting to pH 6.8, 25% of the payload is released within 2h. Cell viability studies indicate that pH-sensitive DMAEMA/HEMA nanoparticles are not cytotoxic and may be used as an efficient, feedback-regulated drug delivery carrier.

Publication types

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

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry
  • Cell Survival / drug effects*
  • Delayed-Action Preparations / administration & dosage*
  • Delayed-Action Preparations / chemistry
  • Diffusion
  • Drug Carriers / chemistry
  • HeLa Cells
  • Humans
  • Materials Testing
  • Methacrylates / chemistry*
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use*
  • Nanoparticles / ultrastructure
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Particle Size

Substances

  • Antineoplastic Agents, Phytogenic
  • Delayed-Action Preparations
  • Drug Carriers
  • Methacrylates
  • hydroxyethyl methacrylate
  • 2-(dimethylamino)ethyl methacrylate
  • Paclitaxel