Evaluation of carboxymethylpullulan as a novel carrier for targeting immune tissues

Purpose. To demonstrate the potential of carboxymethylpullulan (CMPul) as a carrier for targeting immune tissues, and to find whether immune tissues c ould be set as the target of an immunosuppressant to treat autoimmune disea ses. Methods. The biodistribution of CMPul was investigated to evaluate its pote ncy as a carrier for targeting immune tissues. Furthermore, an immunosuppre ssant-CMPul conjugate was prepared and its suppressive effect on rat adjuva nt arthritis was examined. Results. The disappearance rate of H-3-labeled CMPul from the blood circula tion was much slower than that of H-3-labeled pullulan (Pul) after intraven ous injection to normal rats. The concentration of H-3-labeled CMPul in the spleen and lymph nodes was much higher than that of H-3-labeled Pul at 24 hours after the injection, whereas the concentration of H-3-labeled CMPul i n the liver was significantly lower than that of H-3-labeled Pul. A similar targeting property of H-3-labeled CMPul for these immune tissues was obser ved in arthritic rats. A conjugate composed of a novel immunosuppressant PA -48153C and CMPul showed a suppressive effect on rat adjuvant arthritis jud ging from a reduction of the arthritic index and spleen weight and an incre ase of body weight. Conclusions. CMPul is expected to be a promising carrier for targeting immu ne tissues with an immunosuppressant to enable treatment of autoimmune dise ases.