Investigation of new 32P-CP-PLLA microparticle in the treatment of pancreatic cancer mice

Objectives L-Polylactide (PLLA) is a good biocompatibility and biodegradable polymer. ³²P-chromic phosphate-L-polylactide (³²P-CP-PLLA) microparticle is a new control release preparation of the therapy radionuclide ³²P. The objective of the study is to compare systemic distribution and effective therapy of ³²P-CP colloidal and new ³²P- CP-PLLA microparticle.

Methods ³²P-CP-PLLA microparticles were prepared by SED process. The microparticle exhibits as a cylinder, the diameter length, height and mass were 0.85~0.9 mm, 2.2~2.5mm and 0.9~1.1mg, respectively. Nude mice with pancreatic cancerxenograft were divided into seven groups randomly. Group A: 3.7MBq ³²P-CP colloidal; group B: 3.7MBq ³²P-CP-PLLA microparticles; group C: 7.4MBq ³²P-CP-PLLA microparticles; group D: 18.5MBq ³²P-CP-PLLA microparticles; group E: 37MBq ³²P-CP-PLLA microparticles; group F: 74MBq ³²P-CP-PLLA; group G: untreated mice. The tumor and other interesting organs of group A and B were counted for radioactivity at 24h, 8d and 16d post implantation. Body weight, complete blood count and tumor volume of each group were monitoredfor 4 weeks post implantation.

Results Maximum tolerated dose of the microparticle was determined as 3700 MBq/kg. The radioactivity in the ³²P-CP-PLLA microparticles were restrained fully in the tumor, while ³²P colloid may diffuse from tumor to other organs after injecting into tumors. Body weight andplatelet counts recover to baseline value by 4 weeks.

Conclusions The new microparticle could restrain diffusion of colloidal ³²P from tumor to the other outer-tumor organs and deposit colloidal ³²P in the tumors for longer time, therefor decrease the systemic distribution and side effect. Tumor growth control was successfully achieved with the new dosage form.

Research Support National 863 Program 2007AA02Z471