Polyethylene oxide-chitosan-doxorubicin/polycaprolactone-chitosan-curcumin pH-sensitive core/shell nanofibrous mats for the treatment of breast cancer: Fabrication, characterization and in vitro and in vivo evaluation.

The main objective of this study was to fabricate a pH-sensitive drug carrier based on coaxial electrospun nanofibrous mats for concurrent local delivery of hydrophilic and hydrophobic anti-cancer drugs to improve the anti-tumor efficacy on breast cancer. Therefore, co-axial electrospinning technique was applied to prepare polyethylene oxide-chitosan/polycaprolactone-chitosan (PEO-CS/PCL-CS) pH-sensitive core-shell nanofibers. Doxorubicin hydrochloride (DOX, hydrophilic anti-cancer) and curcumin (CUR, hydrophobic anticancer) were loaded into core and shell sections of the fabricated pH-sensitive coaxial nanofibers, respectively. Their structure and morphology were analyzed via SEM, TEM, TGA, and FTIR techniques. The results of in vitro release analysis indicated that the release of DOX and CUR from the fabricated nanofibers was strongly depended on pH. The combined effects of the two drugs on MCF-7 cell inhibition, as measured by the MTT assay, revealed that the 1:5 ratio of DOX to CUR resulted in a CI of 0.00492, showing the strongest synergistic effect. The results of in-vivo studies indicated that the PEO-CS-DOX/PCL-CS-CUR pH-sensitive core-shell nanofibers possessed remarkable anti-tumor efficacy. As a result, PEO-CS-DOX/PCL-CS-CUR pH-sensitive core-shell nanofibrous mats with pH-responsive and sustainable and controllable manner could improve the local anti-tumor efficacy on breast cancer via inhibiting the side effects of free DOX and CUR drugs.