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 could be set as the target of an immunosuppressant to treat autoimmune diseases.Methods. The biodistribution of CMPul was investigated to evaluate its potency as a carrier for targeting immune tissues. Furthermore, an immunosuppressant-CMPul conjugate was prepared and its suppressive effect on rat adjuvant arthritis was examined.Results. The disappearance rate of ³H-labeled CMPul from the blood circulation was much slower than that of ³H-labeled pullulan (Pul) after intravenous injection to normal rats. The concentration of ³H-labeled CMPul in the spleen and lymph nodes was much higher than that of ³H-labeled Pul at 24 hours after the injection, whereas the concentration of ³H-labeled CMPul in the liver was significantly lower than that of ³H-labeled Pul. A similar targeting property of ³H-labeled CMPul for these immune tissues was observed in arthritic rats. A conjugate composed of a novel immunosuppressant PA-48153C and CMPul showed a suppressive effect on rat adjuvant arthritis judging from a reduction of the arthritic index and spleen weight and an increase of body weight.Conclusions. CMPul is expected to be a promising carrier for targeting immune tissues with an immunosuppressant to enable treatment of autoimmune diseases.