Electrospray fabrication of doxorubicin-chitosan-tripolyphosphate nanoparticles for delivery of doxorubicin

This work focused on a new technique for the preparation of doxorubicin (DOX) loaded chitosan (CS) nanoparticles (DOX-CS) - formation by electrospray ionization in the presence of tripolyphosphate (TPP) as the stabilizer. The working distance, needle gauge, flow rate, stirring rate, electrospraying voltage and DOX to CS molar ratio were sequentially and individually optimized and found to be a 26 gauge needle, an applied voltage of 13 kV, a flow rate of 0.5 mL/h, a working distance of 8 cm and a stirring rate of 400 rpm. The incorporation of chemically unchanged DOX with the CS into the particles was ascertained by Fourier transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Under these optimized conditions, the DOX-CS particles were found to be nanoparticles of approximately 300 - 570 (dry particles) or 530 - 870 nm diameter (hydrated particles), with a PDI and SPAN polydispersity indices of 0.97 - 0.82 and 0.62 - 0.64, respectively, for initial DOX loading levels of 0.25 - 1%, as determined by SEM and particle size analyzer, respectively. Moreover, a high encapsulation efficiency (EE) of DOX into the nanoparticles was attained, ranging from 63.4 to 67.9% EE at 1 to 0.25% DOX loading. Finally, the in vitro DOX release behaviors of the DOX-CS particles revealed a prolonged release of DOX over at least seven hours.