Facile preparation of heparin/CaCO3/CaP hybrid nano-carriers with controllable size for anticancer drug delivery

Abstract

A facile method to prepare inorganic/organic hybrid heparin/CaCO3/CaP nanoparticles for drug delivery was developed. The heparin/CaCO3/CaP nanoparticles were prepared by the co-precipitation of Ca2+ ions with carbonate and phosphate ions in the presence of heparin. The effects of ion concentrations on the particle size and properties of the nanoparticles were investigated. The dynamic light scattering (DLS) particle size analysis and scanning electron microscopy (SEM) observation showed that the mean size of the hybrid nanoparticles could be controlled at less than 50nm in the dried state through adjusting the concentrations of the inorganic ions. Fourier transform infrared (FTIR) spectroscopy indicated that the crystallization of CaCO3 could be suppressed with the presence of phosphate ions in the co-precipitation system. X-ray photoelectron spectroscopy (XPS) showed that the heparin content in the surface layer of heparin/CaCO3/CaP hybrid nanoparticles decreased with the increasing ion concentrations during the nanoparticle preparation. The drug loading and release properties of the hybrid nanoparticles with different sizes and different compositions were studied. The in vitro cellular cytotoxicity indicated that blank hybrid nanoparticles had good biocompatibility, whereas doxorubicin hydrochloride (DOX) loaded nanoparticles exhibited a strong cell inhibition effect, indicating that the heparin/CaCO3/CaP hybrid nanoparticles could be promising carriers for drug delivery.