生物可分解性多功能微粒體於肝癌栓塞治療之研究

Abstract

The purpose of this study is to develop biodegradable microspheres which combined with chemotherapy and radiotherapy for transcatheter arterial embolization/chemoembolization (TAE/TACE) or local injectable forms. By locally and slowly release of chemotherapeutic agents, the effect of cancer treatment can be extended. In the experiment, we used biodegradable and biocompatible polymer Poly(D,L-lactide-co-glycolide)(PLGA) to prepare micron particles. Through double emulsion, the microspheres contain water-soluble polymers, including carboxymethylcellulose sodium salt, poly(sodium 4-styrenesulfonate), poly(4-styrenesulfonic acid) ammonium salt solution and Poly(vinylsulfonic acid, sodium salt) solution. The functional groups of those polymers will dissociate into -SO3- or -COO- in water. Doxorubicin can be loaded into the beads using an interaction process between the protonated primary amine on the drug and the negatively charged groups. The microspheres could embedded with 188Re-tin-colloid in the pore spaces which on or in the particles. Experimental results show that 50 mg PVSA/PLGA microspheres absorbed 2.5 mg doxorubicin within an hour had the best absorption efficiency. Microspheres were embedded with 188Re-tin-colloid and performed in a rat hepatocellular carcinoma model. NanoSPECT/CT imaging and bio-distribution showed the microspheres were still in the liver after 72 hours. The tumor growth was more profoundly inhibited by treatment with Re/DOX@MS than others by ultrasonography during 4 weeks observation period. The microspheres may offer the advantage of locally injection or embolization. In the future, the drug delivery system for cancer radiotherapy combined with chemotherapy using a biodegradable PLGA microspheres consisting of therapeutic radionuclide and chemotherapeutic drugs could maximize their effects on hepatocellular carcinoma.