The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology
| Autor: | Ronald K. June, Martin Lotz, Steven F. Dowdy, Akiko Eguchi, Sabrina E. Dinkel, Sarah E. Mailhiot, Matthew A. Thompson |
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| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
Technology 030213 general clinical medicine viruses Biomedical Engineering Physical Therapy Sports Therapy and Rehabilitation Osteoarthritis Pharmacology Hiv 1 tat Mice 03 medical and health sciences Transduction (genetics) Chondrocytes 0302 clinical medicine Intra articular Animals Immunology and Allergy Medicine Tat peptide Clinical Research papers 030203 arthritis & rheumatology business.industry medicine.disease Cartilage Gene Products tat Drug delivery business |
| Zdroj: | Cartilage |
| ISSN: | 1947-6043 1947-6035 |
| Popis: | Objective Intra-articular drug delivery holds great promise for the treatment of joint diseases such as osteoarthritis. The objective of this study was to evaluate the TAT peptide transduction domain (TAT-PTD) as a potential intra-articular drug delivery technology for synovial joints. Design Experiments examined the ability of TAT conjugates to associate with primary chondrocytes and alter cellular function both in vitro and in vivo. Further experiments examined the ability of the TAT-PTD to bind to human osteoarthritic cartilage. Results The results show that the TAT-PTD associates with chondrocytes, is capable of delivering siRNA for chondrocyte gene knockdown, and that the recombinant enzyme TAT-Cre is capable of inducing in vivo genetic recombination within the knee joint in a reporter mouse model. Last, binding studies show that osteoarthritic cartilage preferentially uptakes the TAT-PTD from solution. Conclusions The results suggest that the TAT-PTD is a promising delivery strategy for intra-articular therapeutics. |
| Databáze: | OpenAIRE |
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