Co-delivery of Bcl-2 siRNA and doxorubicin using liposome-incorporated poly(ε-caprolactone) /chitosan nanofibers for the treatment of lung cancer

Abstract

The small interfering RNA (siRNA) and chemotherapeutic drugs-incorporated liposome-nanofiber hybrid delivery system could inhibit tumor growth and decrease the adverse side effects. In the present study, doxorubicin (DOX) anticancer drug and Bcl-2 siRNA have been incorporated into the liposome-embedded chitosan-poly (ethylene oxide)/poly (ε-caprolactone) (CS/PEO/PCL) pH-sensitive nanofibrous hybrid formulation for treating lung cancer. The mean particle size & zeta potential of liposome, DOX-liposome, and DOX-Bcl-2-liposome were 130 ± 10 nm & 27.85 ± 1.65 mV, 155 ± 15 nm & 26.30 ± 1.3 mV, and 195 ± 30 nm &11.31 ± 0.65 mV, respectively. The average diameter of electrospun CS/PEO/PCL/DOX-siRNA-liposome simple and CS/PEO/PCL/DOX-siRNA-liposome core-shell nanofibers was 385 ± 80, and 485 ± 100 nm, respectively. The extended release of DOX and si-RNA (30 days) were achieved from DOX-Bcl-2-liposome-incorporated CS/PEO/PCL core-shell nanofibers. The maximum down-regulation of Bcl-2 siRNA, apoptosis of cancer cells, and reduction in the cell viability of A549 lung carcinoma cells were achieved using DOX-Bcl-2 liposome-incorporated CS/PEO/PCL core-shell nanofibers. The in vivo results indicated the maximum suppress of tumor growth without change in the body weight for the mice treated with DOX-Bcl-2 liposome-incorporated CS/PEO/PCL nanofibers. The obtained results demonstrated that the prepared hybrid delivery system presented a novel effective formulation for treating lung cancer.