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DOTAM derivatives as active cartilage-targeting drug carriers for the treatment of osteoarthritis.
- Source :
-
Bioconjugate chemistry [Bioconjug Chem] 2015 Mar 18; Vol. 26 (3), pp. 383-8. Date of Electronic Publication: 2015 Feb 12. - Publication Year :
- 2015
-
Abstract
- Targeted drug-delivery methods are crucial for effective treatment of degenerative joint diseases such as osteoarthritis (OA). Toward this goal, we developed a small multivalent structure as a model drug for the attenuation of cartilage degradation. The DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide)-based model structure is equipped with the cathepsin D protease inhibitor pepstatin A, a fluorophore, and peptide moieties targeting collagen II. In vivo injection of these soluble probes into the knee joints of mice resulted in 7-day-long local retention, while the drug carrier equipped with a scrambled peptide sequence was washed away within 6-8 h. The model drug conjugate successfully reduced the cathepsin D protease activity as measured by release of GAG peptide. Therefore, these conjugates represent a promising first drug conjugate for the targeted treatment of degenerative joint diseases.
- Subjects :
- Acetamides metabolism
Animals
Arthritis, Experimental drug therapy
Arthritis, Experimental metabolism
Arthritis, Experimental pathology
Cartilage metabolism
Cartilage pathology
Drug Carriers metabolism
Heterocyclic Compounds, 1-Ring metabolism
Mice
Osteoarthritis metabolism
Osteoarthritis pathology
Swine
Acetamides administration & dosage
Cartilage drug effects
Drug Carriers administration & dosage
Drug Delivery Systems methods
Heterocyclic Compounds, 1-Ring administration & dosage
Osteoarthritis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4812
- Volume :
- 26
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Bioconjugate chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25629889
- Full Text :
- https://doi.org/10.1021/bc500557s