A Novel Delivery System for the Combined Use of Natural Ingredients: The Preparation of Berberine Hydrochloride–Matrine Liposomes and Preliminary Exploration of Their Anti-Tumor Activity

Berberine hydrochloride (BH) extracted from Coptis chinensis (CC) and Matrine (MT) separated from Sophora flavescens (SF) are alkaloids with potent anti-bacterial, anti-inflammatory, and anti-tumor effects. Motivated by the clinical practice of using CC and SF together, we aimed to demonstrate that the synergistic application of the natural compounds BH and MT could enhance therapeutic effects and minimize side effects. Two types of liposomes, liposomes containing only BH (BH-LP) and liposomes containing both BH and MT (BH-MT-LP), were successfully prepared via the reverse evaporation method. The liposome preparation process was optimized by single-factor screening and the Box-Behnken experimental design method. The results showed that the liposomes had particle sizes in the range of 222.7 to 235.4 nm, polydispersity indicated in the range of 11.8% to 23.3%, and zeta potentials in the range of -35.9 to -31.1 mv. BH-MT-LP showed superior anti-tumor activity against MDA-MB-231, HepG-2, and HGC-27 cells in vitro. The incorporation of MT effectively promoted the anti-tumor effect of BH, while the controlled release from liposomes further enhanced the therapeutic efficacy of BH. Furthermore, based on the flow cytometry results, we speculated that BH-MT-LP might promote apoptosis by blocking the G1 phase of cells and inducing cell death. In conclusion, BH-MT-LP provides evidence for the combined use of natural compounds as a stable, safe, and practical drug delivery system for the treatment of potential cancers. Meanwhile, the successful preparation for BH-MT-LP also provides a new approach to the combined use of traditional Chinese medicine ingredients.