Sialyl Lewis X-Carboxymethylpullulan Conjugate: A Novel Homing Device to Spleen and Lymph Nodes
| Autor: | Takayoshi Yoshikawa, Masahiro Sakagami, Kazutoshi Horie, Kazuyoshi Masuda, Koichiro Hirano, Hiroshi Hamana, Mitsuru Notoya |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Oligosaccharides
Pharmaceutical Science Spleen Fucose chemistry.chemical_compound medicine Animals Moiety Tissue Distribution Sialyl Lewis X Antigen Glucans Lymph node Pharmacology General Medicine Rats Sialic acid Sialyl-Lewis X medicine.anatomical_structure chemistry Biochemistry Rats Inbred Lew Autoradiography Female Lymph Nodes Lymph Conjugate |
| Zdroj: | Biological and Pharmaceutical Bulletin. 27:1275-1280 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | We have previously found that carboxymethylpullulan (CMPul) conjugated with sialyl Lewis X (Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAc-, 2-3SLex) preferentially accumulates in the lymph nodes and spleen. In the present study, we investigated the structural requirements of the 2-3SLex moiety for this accumulation using rats. Radiolabeled CMPul conjugates with various degrees of substitution (d.s.) of the 2-3SLex moiety were intravenously administered to rats, and their tissue distributions were monitored by radioactivity. When the d.s. was more than 0.5, preferential accumulation in the lymph nodes as well as the spleen was observed. However, when the d.s. was 0.025, little effect of the 2-3SLex moiety was noted. Changes in the carbohydrate structure of 2-3SLex, i.e., a change to alpha2-6-linked sialic acid (Neu5Acalpha2-6Galbeta1-4(Fucalpha1-3)GlcNAc-, 2-6SLex) or an elimination of the fucose (Neu5Acalpha2-3Galbeta1-4GlcNAc-, sialyl N-acethyllactosamine (SLN)), also made the 2-3SLex moiety ineffective. Furthermore, Microautoradiography analyses revealed that 2-3SLex-CMPul was incorporated by particular subsets of macrophages in these tissues, and that CMPul and SLN-CMPul were also located in the same cells to a lesser extent. 2-3SLex-CMPul may be able to serve as a novel drug delivery carrier to target drugs to the peripheral lymphoid tissues. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|