Abstract
Granulocyte colony-stimulating factor (G-CSF) is used to treat neutropenia patients. Although subcutaneous (SC) injections of GCSF are the conventional means to used, the inconvenience, pain, and side effects associated with such injections reduce patient compliance. Oral administration of GCSF is a viable alternative to SC injections, since patients are more receptive to it. Nevertheless, delivering GCSF orally often leads to a low bioavailability owing to its presystemic degradation and inadequate permeation through the intestinal epithelium. To improve the oral bioavailability of GCSF, we described a pH-responsive nanoparticle system composed of chitosan (CS) and DTPA (diethylene triamine pentaacetic acid) modified poly(g-glutamic acid) (γPGA-DTPA). CS, a mucoadhesive polycation, can enhance the intestinal paracellular permeability by transiently opening the tight junctions (TJs) between epithelial cells; DTPA, which can inhibit enzymes degradation by chelating metal cations (such as Ca2+ or Zn2+). The functional nanoparticles composed of CS and γPGA-DTPA has a mucosal adsorption, intestinal enzymes inhibition, and enhancing intestinal absorption of G-CSF, which can be expected to increase drug bioavailability.