pH-responsive nano carriers for doxorubicin delivery

Pharm Res. 2015 Apr;32(4):1249-63. doi: 10.1007/s11095-014-1530-0. Epub 2014 Oct 7.


Purpose: The aim of this study was to design stimuli-responsive nanocarriers for anti-cancer drug delivery. For this purpose, doxorubicin (DOX)-loaded, polysebacic anhydride (PSA) based nanocapsules (NC) were combined with pH-sensitive poly (L-histidine) (PLH).

Method: PSA nano-carriers were first loaded with DOX and were coated with poly L-histidine to introduce pH sensitivity. The PLH-coated NCs were then covered with polyethylene glycol (PEG) to reduce macrophage uptake. The drug release profile from this system was examined in two different buffer solutions prepared as acidic (pH5) and physiological (pH 7.4) media. The physical and chemical properties of the nanocapsules were characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), ultraviolet and visible absorption spectroscopy (UV-VIS), and scanning electron microscopy (SEM). In vitro studies of the prepared nanocapsules were conducted in MDA-MB-231 breast cancer cells.

Results: The results obtained by SEM and DLS revealed that nanocapsules have spherical morphology with an average size of 230 nm. Prepared pH sensitive nanocapsules exhibited pH-dependent drug release profile and promising intracellular release of drug. PEGylation of nanoparticles significantly prevented macrophage uptake compared to non-PEGylated particles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anhydrides / chemistry*
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Decanoic Acids / chemistry*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Histidine / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Nanocapsules / chemistry*
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Surface Properties


  • Anhydrides
  • Antibiotics, Antineoplastic
  • Decanoic Acids
  • Drug Carriers
  • Nanocapsules
  • Poly (sebacic anhydride)
  • Polyethylene Glycols
  • Histidine
  • Doxorubicin