PH-responsive co-delivery of doxorubicin and saffron via cross-linked chitosan/laponite RD nanoparticles for enhanced-chemotherapy

Abstract

Combining natural antioxidants with synthetic anticancer agents is a helpful approach in chemotherapy to reduce side effects and enhance the effectiveness of drugs. Saffron extract (SAF), a natural antioxidant with anti-cancer properties, bears a protective effect against doxorubicin-induced toxicity. Co-delivery of doxorubicin (DOX), a known anticancer agent, and SAF using nanotechnology, can be helpful to achieve a highly effective chemotherapy result. This study aimed to design cross-linked chitosan/laponite RD (CS/LP®) nanoparticles for co-encapsulation of DOX and SAF. The results indicated a high encapsulation efficiency of DOX (≥83%) and SAF (≥60%) for synthesized nanocarriers. These carriers exhibited a highly controllable pH-responsive release behavior. The release of DOX and SAF remarkably increased by decreasing pH from neutral (pH 7.4) to acidic (pH 5.5). The effects of cross-linked CS content were evaluated on the release properties. An increase in cross-linked CS content imposed a sustained release behavior by decreasing the release rate. The kinetic studies were used to confirm the release mechanisms. In vitro tests performed high cytotoxicity for doxorubicin/saffron-loaded nanoparticles against MDA-MB-231 cells. The MTT assay demonstrated no cytotoxicity for CS/LP® nanoparticles confirming its biocompatibility. The DOX/SAF-loaded nanocarriers exhibited antibacterial activity against Gram-negative and Gram-positive bacteria. • Doxorubicin and saffron were successfully co-encapsulated into cross-linked CS/LP® with high encapsulation efficiency. • The cross-linked CS/LP® nanoparticles showed simultaneous release for doxorubicin and saffron with high pH-responsive and controllable properties. • Increasing cross-linked CS content endowed sustained release by a remarkable reduction of release rate. • In vitro tests performed high cytotoxicity for doxorubicin/saffron-loaded nanoparticles against breast cancer cell lines.