Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations
Program in Molecular Medicine
Biochemistry | Biomaterials | Biomedical Devices and Instrumentation | Immunopathology | Immunoprophylaxis and Therapy | Molecular Biology | Therapeutics | Translational Medical Research
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.
Biomedical engineering, Drug delivery, Implants, Translational research
DOI of Published Version
Nat Mater. 2019 Aug;18(8):892-904. doi: 10.1038/s41563-019-0377-5. Epub 2019 Jun 24. Link to article on publisher's site
Farah S, Greiner DL, Anderson DG. (2019). Long-term implant fibrosis prevention in rodents and non-human primates using crystallized drug formulations. Program in Molecular Medicine Publications. https://doi.org/10.1038/s41563-019-0377-5. Retrieved from https://escholarship.umassmed.edu/pmm_pp/132