Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations
| Autor: | Hok Hei Tam, Daniel G. Anderson, Dale L. Greiner, Hye Jung Han, Marissa Griffin, Katy N. Olafson, Robert Langer, Peter Müller, James J. McGarrigle, Adam Graham, Shady Farah, Piotr S. Kowalski, Joshua C. Doloff, Jose Oberholzer, Jennifer Hollister-Lock, Ashley Meng, Malia McAvoy, Keval Vyas, Gordon C. Weir, Atieh Sadraei |
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| Rok vydání: | 2019 |
| Předmět: |
Drug
Modern medicine Drug Compounding media_common.quotation_subject Rodentia 02 engineering and technology 010402 general chemistry 01 natural sciences Article Colony stimulating factor 1 receptor Fibrosis In vivo medicine Animals General Materials Science media_common Chemistry Macrophages Mechanical Engineering Prostheses and Implants General Chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics medicine.disease Controlled release 0104 chemical sciences Mechanics of Materials Delayed-Action Preparations Drug delivery Implant 0210 nano-technology Biomedical engineering |
| Zdroj: | Nature materials |
| ISSN: | 1476-4660 1476-1122 |
| DOI: | 10.1038/s41563-019-0377-5 |
| Popis: | Implantable medical devices have revolutionized modern medicine. However, immune-mediated foreign body response (FBR) to the materials of these devices can limit their function or even induce failure. Here we describe long-term controlled-release formulations for local anti-inflammatory release through the development of compact, solvent-free crystals. The compact lattice structure of these crystals allows for very slow, surface dissolution and high drug density. These formulations suppress FBR in both rodents and non-human primates for at least 1.3 years and 6 months, respectively. Formulations inhibited fibrosis across multiple implant sites—subcutaneous, intraperitoneal and intramuscular. In particular, incorporation of GW2580, a colony stimulating factor 1 receptor inhibitor, into a range of devices, including human islet microencapsulation systems, electrode-based continuous glucose-sensing monitors and muscle-stimulating devices, inhibits fibrosis, thereby allowing for extended function. We believe that local, long-term controlled release with the crystal formulations described here enhances and extends function in a range of medical devices and provides a generalized solution to the local immune response to implanted biomaterials. Foreign body response can result in failure of biomaterials in vivo. Solvent-free crystals containing anti-fibrotic drugs now show the potential for long-term inhibition of fibrosis on a number of implantable devices in rodents and non-human primates. |
| Databáze: | OpenAIRE |
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