Formulation, Preparation and Evaluation of Nanostructured Lipid Carrier Containing Naringin and Coix Seed Oil for Anti-Tumor Application Based on “Unification of Medicines and Excipients”

摘要

Background: “Unification of medicines and excipients” is the special principle which means fatty oil with pharmacodynamic activity derived from traditional Chinese medicine are taken as liquid lipids in perparation for dual-drug delivery, which improve the treatment effect and reduce unnecessary excipients. Purpose: The aim of this study was to prepare a nanostructured lipid carrier (NLC) with naringin (NG) containing coix seed oil (CSO) as liquid lipid based on the theory (NCNLC) in order to achieve synergistic antitumor activity against hepatocellular carcinoma. Methods: We developed NCNLCs using ultrasonic melt-emulsification method. The antitumor effect in vivo/in vitro and drug release ability were compared to NLC prepared with conventional liquid lipids: neodecanoate triglycerides (NDNLC) and oleic acid (NONLC). Results: Transmission electron microscopy showed that NCNLCs had a well-defined spherical shape, small size, and narrow polydispersity index. Importantly, the release of drugs from NDNLCs and NONLCs was slower than NCNLCs. In the cell study, the result showed a significantly greater antiproliferative effect towards HepG2 cells, and?the half-maximal inhibitory concentration of NCNLCs was 3.24-fold, 1.70-fold and 1.52-fold lower to that of free drug, NDNLCs and NONLCs, respectively. Moreover, NCNLCs significantly induced HepG2 cells apoptosis by being 2.12-fold and 9.28-fold higher to that of NDNLCs and NONLCs, respectively. In the study of antitumor efficacy in vivo, the synergistic effect of NCNLCs formulation showed markedly enhanced antitumor efficacy in a xenograft model of liver cancer. Conclusion: The advantages of “unification of medicines and excipients” in formulation characters, drug release and synergistic antitumor effect provide a new idea for the application of the fatty oil of traditional Chinese medicine in the nano-drug delivery for cancer therapy.