Oral Administration of Liposome-Apatinib and Locally Delivery of Docetaxel/MPEG-PCL by Fibrin Glue Synergistically Improve Therapeutic Effect in Colorectal Cancer

Colorectal cancer is one of the most common and malignant cancer in the world wide. Recently, combination of target therapy and chemotherapy has generated new promise for colorectal cancer. Apatinib mesylate is a novel and highly selective VEGFR-2 inhibitor, presented with an outstanding activity of anti-angiogensis, which has the potential for treating various tumors. As a traditional chemotherapeutic drug, docetaxel (Taxotere) is a widely used semisynthetic taxoid in solid tumors. In this study, Liposome and Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) were constructed as drug delivery system for the delivery of apatinib (Lipo-Apa) and docetaxel (DOC/M), respectively. Co-administration of Lipo-Apa and DOC/M showed synergistically effects on inhibiting cell proliferation and inducing cell apoptosis of CT26 cells in vitro. Moreover, fibrin glue, as a biocompatible adherent hemostat, was used as a kind of vehicle for locally delivery of DOC/M in animal models, for achieving locally high concentration and prolonging releasing time. Combination of Lipo-Apa by gavage and locally delivery of DOC/M showed significantly improved anti-tumor activity in a subcutaneous xenograft model as well as in the abdominal metastasis model of colorectal cancer. In addition, promoted tumor apoptosis, inhibited proliferation and decreased tumor angiogenesis were presented by the co-administration. Finally, our study suggested that combination of oral administration of Lipo-Apa and locally delivery of DOC/M by fibrin glue, has the potential to be applied clinically in colorectal cancer therapy.