title: "Smart tattoo" glucose biosensors and effect of coencapsulated anti-inflammatory agents.
abstract: BACKGROUND
  Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres.
  
  
  METHODS
  The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation.
  
  
  RESULTS
  The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0-50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site.
  
  
  CONCLUSIONS
  The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as "smart tattoo" glucose sensors with increased functional longevity.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India. rsrivasta@iitb.ac.in
authors.forename: Rohit
authors.initials: R
authors.lastname: Srivastava
authors.forename: Rahul Dev
authors.initials: RD
authors.lastname: Jayant
authors.forename: Ayesha
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McShane
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D001185:Artificial Intelligence; D015374:Biosensing Techniques / Q000379:methods; D001786:Blood Glucose / Q000032:analysis* / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology; D004338:Drug Combinations; D004339:Drug Compounding; D005456:Fluorescent Dyes / Q000494:pharmacology; D005949:Glucose Oxidase / Q000008:administration & dosage* / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008863:Microspheres; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000464:Alginates; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D004338:Drug Combinations; D005456:Fluorescent Dyes; D006603:Hexuronic Acids; D004008:Diclofenac; D003907:Dexamethasone; D020723:Glucuronic Acid; D005949:Glucose Oxidase