Polymer-controlled core–shell nanoparticles: a novel strategy for sequential drug release

Abstract

Sequentially-controlled drug release is required in cancer combination chemotherapy treatment. With the aim of co-delivering multiple drugs with different targets, immiscible and miscible liquids were utilized to fabricate PVP/PLGA and PCL/PLGA nanoparticles with a distinct core–shell structure by coaxial electrospray. It allows the fabrication of core–shell nanoparticles with different inner core characteristics of hydrophilic properties in one single step. The anti-angiogenesis agent combretastatin A4 (CA4) and doxorubicin (DOX) were each encapsulated separately in the core and shell parts of dual-drug nanoparticles. Both hydrophobic and hydrophilic drugs can be encapsulated into the coaxial-electrospray particles effectively, and the encapsulation efficiencies of drugs, particularly the hydrophilic ones, are over 90%. The endothelial cell and tumor cell co-culture systems were utilized to testify the performances of different nanoparticles against cytotoxicity, cellular apoptosis and VEGF and HIF-1α protein expressions in vitro. The melanoma cells B16-F10 and human umbilical vein endothelial cells (HUVECs) were sequentially targeted and killed by CA4 and DOX from these two kinds of nanoparticles. It demonstrated two different sequential drug release profiles in vitro. PVP/PLGA nanoparticles, with hydrophilic inner cores, presented a faster and higher drug release than that of PCL/PLGA nanoparticles, due to the better affinity of PVP polymers with the incubation media. These results suggested that the release rates and profiles of dual drug loaded particles can be tailored and tuned by choosing core polymers with different characteristics of hydrophilic properties. Therefore, the clinical treatment necessity can be fulfilled and the improvement of drug efficiency is promising in tumor combination chemotherapy.