Molecular transport in articular cartilage — what have we learned from the past 50 years?
| Autor: | Chris D. DiDomenico, Lawrence J. Bonassar, Marianne Lintz |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Cartilage
Articular 0301 basic medicine Pore size 0206 medical engineering Articular cartilage 02 engineering and technology Osteoarthritis Bone matrix 03 medical and health sciences Rheumatology medicine Molecular Transport Animals Humans Inflammatory factors business.industry Arthritis Cartilage Biological Transport medicine.disease 020601 biomedical engineering 030104 developmental biology medicine.anatomical_structure Antirheumatic Agents Drug Design Biophysics business |
| Zdroj: | Nature Reviews Rheumatology. 14:393-403 |
| ISSN: | 1759-4804 1759-4790 |
| Popis: | Developing therapeutic molecules that target chondrocytes and locally produced inflammatory factors within arthritic cartilage is an active area of investigation. The extensive studies that have been conducted over the past 50 years have enabled the accurate prediction and reliable optimization of the transport of a wide variety of molecules into cartilage. In this Review, the factors that can be used to tune the transport kinetics of therapeutics are summarized. Overall, the most crucial factor when designing new therapeutic molecules is solute size. The diffusivity and partition coefficient of a solute both decrease with increasing solute size as indicated by molecular mass or by hydrodynamic radius. Surprisingly, despite having an effective pore size of ~6 nm, molecules of ~16 nm radius can diffuse through the cartilage matrix. Alteration of the shape or charge of a solute and the application of physiological loading to cartilage can be used to predictably improve solute transport kinetics, and this knowledge can be used to improve the development of therapeutic agents for osteoarthritis that target the cartilage. |
| Databáze: | OpenAIRE |
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