Preparation And Anti - Tumor Effect Of Paclitaxel And Hypericin Supramolecule Inclusion Compound

Paclitaxel (PTX) is one of clinical chemotherapy drugs as the first-line drug. It has been reported that is used to chemical treat well with breast and ovarian cancer of patients. Paclitaxel has been a controversial drug due to some deficiencies of it, such as, poor solubility in water, low bioacailability and side effects, although it has been used extensively. Hypericin (HYP), is a kind of natural photosensitizer, can produce peroxides activated by light. HYP induced the tumor cell apoptosis and inhibit its growth. It has specific affinity to tumor necrosis tissue. Therefore, it has been commonly used to optical diagnosis of tumor tissue in clinic. However, HYP is hardly soluble in water. In the present study, the complexations of cyclodextrin polymers with PTX and HYP have been deeply studied to development of new anti-tumor drug that target to the tumor necrosis tissue. The main contents and results are as follows:(1) Cyclodextrin polymers were prepared with β-cyclodextrin and epichlorohydrin, and identified by IR and1H-NMR. The inclusion complex of PTX-HYP-CDP was prepared by grinding method. The encapsulation efficiency and yield coefficient were determined by ultraviolet-visible spectrophotometry method.(2) The inclusion complex of PTX-HYP-CDP was characterized by the methods of infrared absorption spectroscopy (IR), nuclear magnetic resonance and X-ray diffraction (XRD). It was identified that the PTX-HYP-CDP inclusion complexes were formed.(3) The technology conditions of preparation were screened by the orthogonal test. The multiple factors including molar ratio of paclitaxel, hypericin, and cyclodextrin polymers, time, temperature and concentration of solvent were investigated in the inclusion process to optimize the preparation conditions of PTX-HYP-CDP.The result showed that the optimum preparation conditions for inclusion were established as follows:the molar ratio of PTX, HYP and CDP was1:1:4, time was120min, temperature was30℃and concentration of methyl alcohol was50%.Study on the stability of PTX-HYP-CDP inclusion complex under high temperature, humidity and ultraviolet irradiation conditions. The result showed that the PTX-HYP-CDP inclusion complex has the high stability into high temperature and light, while sensitive to humidity.(4) MTT assay was used to determine the inhibitory rate of PTX-HYP-CDP on SMMC7721cells; The morphological changes of SMMC7721cells were detected with AO/EB dye.In this study, the inclusion complex of PTX-HYP-CDP was successfully prepared. The technology and stability of PTX-HYP-CDP were investigated in the present study. The result also showed that treatment with PTX-HYP-CDP has the effect on tumor growth. The study provides the good foundation on the development of the new preparation of PTX.