Many macromolecular
antitumor drugs were developed based on the enhanced permeability and retention (EPR) effect, for example,
albumin-bound paclitaxel nanoparticles (nab-PTX and
Abraxane) and
pegylated liposomal doxorubicin (
Doxil). However, these EPR effect-based therapeutic systems are less effective in malignant
tumors with low vascular permeability, such as pancreatic
tumors. Because the EPR effect depends on nanoparticles' size, we first determined nanoparticles' size associated with a high
tumor-targeting rate in a human pancreatic
tumor xenograft model with low vascular permeability.
Abraxane appears to behave as an
albumin monomer (7 nm) in the blood circulation following
intravenous injection. The in vitro and in vivo
tumor-targeted delivery and antitumor activity of PTX-loaded
albumin nanoparticles were significantly improved by optimizing the mean nanoparticle diameter to 30 nm. Furthermore,
nitric oxide was added to 30 nm PTX-loaded
albumin nanoparticles to examine the feasibility of
albumin nanoparticles as a platform for multiple drug delivery. Their antitumor effect was evaluated in an orthotopic
transplantation mouse model of a human pancreatic
tumor. The
nitric oxide PTX-loaded 30 nm
albumin nanoparticle treatment on model mice achieved a significantly higher survival rate than
Abraxane treatment. These findings suggest that 30 nm
albumin nanoparticles have a high
therapeutic effect as a useful platform for multiple drugs against human pancreatic
tumors.