Evaluation of carboxymethylpullulan as a novel carrier for targeting immune tissues.
OBJECTIVE
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.
Masuda
K
K
Shionogi Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan. kazuyoshi.masuda@shionogi.co.jp
Sakagami
M
M
Horie
K
K
Nogusa
H
H
Hamana
H
H
Hirano
K
K
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005936:Glucans / Q000737:chemistry* / Q000493:pharmacokinetics; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D007262:Infusions, Intravenous; D011753:Pyrones / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution
D004337:Drug Carriers; D005936:Glucans; D007166:Immunosuppressive Agents; D011753:Pyrones; C410955:carboxymethylpullulan; C088446:pironetin