Studies On Tumor Targeting And PH-sensitive Polyelectrolyte Complex Nanoparticles For Oral Administration

This article was mainly studied the oral drug delivery system as follows:First, HA-PTX conjugates were synthesized by conjugating the paclitaxel (PTX) tohyaluronic acid (HA) through esterification reaction under the catalysis ofdicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP). Highperformance liquid chromatography (HPLC), fourier infrared spectrometer (FT-IR),nuclear magnetic resonance apparatus (1H-NMR), transmission electron microscopy(TEM), laser particle size analyzer (LPSA) and fluorescence spectrum were used toexamine the content of PTX, structure, composition, morphology, zeta potential andcritical micelle concentration (CMC) of the HA-PTX conjugates and NPs. Resultsshow that HA-PTX conjugates with the PTX content of10.6wt%were successfullysynthesized, which could self-assemble into NPs in aqueous solution with paclitaxelfor nuclear and hyaluronic acid for shell with the size of80nm. The pKa of HA-PTXconjugates is about2.1. CMC of HA-PTX NPs was1×10-3mg/mL.For another, polyelectrolyte complex nanoparticles (CS/HA-PTX CNPs) wereprepared by CS and HA-PTX NPs via electrostatic reaction. FT-IR, TEM, LPSA wasused to characterize its structure, morphology, particle size and distribution. In vitrodrug release from CS/HA-PTX CNPs was examined by dynamic dialysis method. Invitro cellular uptake and cytotoxicity were investigated used NIH-3T3cells andHepG2cells as a model cell lines. Ex vivo biodistribution of drug was investigatedused the Balb/c mice bearing Ehrlich ascites tumor. Results shown that, CS/HA-PTXCNPs could avoid the breakage of eater bond in HA-PTX NPs at acidic fasting pHconditions of the stomach. HA-PTX NPs were found to be stable in the blood andreleased drug in the tumor tissue. HA-PTX NPs with the showed increased extent ofcellular uptake for HepG2cells than free PTX and exhibited a quite cytotoxicity butlower side effects than PTX. The concentration of PTX accumulated in the tumor sitesafter oral administration of CS/HA-PTX CNPs was higher than that of free PTX.Therefore, the CS/HA-drug CNPs developed in this work could be employed as apotential carrier for the oral delivery of hydrophobic drug.