title: Local release of masitinib alters in vivo implantable continuous glucose sensor performance.
abstract: Continuous glucose monitoring (CGM) sensors are often advocated as a clinical solution to improve long-term glycemic control in the context of diabetes. Subcutaneous sensor inflammatory response, fouling and fibrous encapsulation resulting from the host foreign body response (FBR) reduce sensor sensitivity to glucose, eventually resulting in sensor performance compromise and device failure. Several combination device strategies load CGM sensors with drug payloads that release locally to tissue sites to mitigate FBR-mediated sensor failure. In this study, the mast cell-targeting tyrosine kinase inhibitor, masitinib, was released from degradable polymer microspheres delivered from the surfaces of FDA-approved human commercial CGM needle-type implanted sensors in a rodent subcutaneous test bed. By targeting the mast cell c-Kit receptor and inhibiting mast cell activation and degranulation, local masitinib penetration around the CGM to several hundred microns sought to reduce sensor fibrosis to extend CGM functional lifetimes in subcutaneous sites. Drug-releasing and control CGM implants were compared in murine percutaneous implant sites for 21 days using direct-wire continuous glucose reporting. Drug-releasing implants exhibited no significant difference in CGM fibrosis at implant sites but showed relatively stable continuous sensor responses over the study period compared to blank microsphere control CGM implants.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: M
authors.initials: M
authors.lastname: Avula
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: D
authors.initials: D
authors.lastname: Jones
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Rao
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: D
authors.initials: D
authors.lastname: McClain
authors.affiliation: Associated Regional and University Pathologist Laboratories, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: McGill
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA; Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: david.grainger@utah.edu.
authors.forename: D W
authors.initials: DW
authors.lastname: Grainger
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA; Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: F
authors.initials: F
authors.lastname: Solzbacher
mesh_terms: D000818:Animals; D001549:Benzamides; D015374:Biosensing Techniques / Q000295:instrumentation; D001786:Blood Glucose / Q000032:analysis* / Q000187:drug effects*; D015190:Blood Glucose Self-Monitoring / Q000295:instrumentation*; D004343:Drug Implants / Q000008:administration & dosage*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines; D019736:Prostheses and Implants; D011725:Pyridines; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000008:administration & dosage*
chemical_list: D001549:Benzamides; D001786:Blood Glucose; D004343:Drug Implants; D010880:Piperidines; D011725:Pyridines; D013844:Thiazoles; C526575:masitinib
keywords: Encapsulation; Foreign body response (FBR); Local drug delivery; Mast cells (MC); Subcutaneous murine implants; Tyrosine kinase inhibitor (TKI)