Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor, masitinib.
The host foreign body response (FBR) adversely effects the performance of numerous implanted biomaterials especially biosensors, including clinically popular glucose-monitoring sensors. Reactive formation of a fibrous capsule around implanted sensors hinders the transport of essential analytes to the sensor from the surrounding tissue, resulting in loss of glucose response sensitivity and eventual sensor failure. Several strategies have sought to mitigate the foreign body response's effects on CGM sensors through the use of local delivery of pharmaceuticals and biomolecules with limited success. This study describes release of a tyrosine kinase inhibitor - masitinib - from the sensor implant to target tissue resident mast cells as key mediators of the FBR. Model implants are coated with a composite polymer hydrophilic matrix that rapidly dissolves upon tissue implantation to deposit slower-degrading polymer microparticles containing masitinib. Matrix dissolution limits coating interference with sensor function while establishing a local controlled-release delivery depot formulation to alter implant tissue pharmacology and addressing the FBR. Drug efficacy was evaluated in a murine subcutaneous pocket implant model. Drug release extends to more than 30 days in vitro. The resulting FBR in vivo, evaluated by implant capsule thickness and inflammatory cell densities at 14, 21, and 28 days, displays statistically significant reduction in capsule thickness around masitinib-releasing implant sites compared to control implant sites.
Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
Mahender Nath
MN
Avula
Archana Nagaraja
AN
Rao
Lawrence D
LD
McGill
David William
DW
Grainger
Florian
F
Solzbacher
D000818:Animals; D001549:Benzamides; D001672:Biocompatible Materials / Q000737:chemistry*; D015374:Biosensing Techniques; D005549:Foreign-Body Reaction / Q000276:immunology* / Q000517:prevention & control; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
D001549:Benzamides; D001672:Biocompatible Materials; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013844:Thiazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C526575:masitinib
Biomedical implants; Continuous glucose monitoring sensors; Foreign body response; Local drug delivery; Mast cells; Tyrosine kinase inhibitor