In vitro and in vivo evaluation of anti-inflammatory agents using nanoengineered alginate carriers: towards localized implant inflammation suppression.
The aim of this research was to develop nanoengineered alginate microspheres for localized delivery of anti-inflammatory drugs (dexamethasone and diclofenac sodium) for implantable "Smart tattoo" glucose biosensor used for continuous glucose monitoring. The formulation was prepared and characterized for in vitro drug release from uncoated and polyelectrolyte-coated microparticles. Biocompatibility was then tested using L929 cell-line; pilot in vivo studies with Sprague-Dawley (SD) rat subjects were performed to test the suppression of inflammation and fibrosis associated with implantation and was analyzed using standard hematoxylin and eosin staining method. The drug-loaded microspheres were able to deliver the drug for 30 days at a controlled rate with zero-order kinetics. The layer-by-layer self-assembly technique was used to effectively limit the burst release of drug from the matrix. Cell culture studies prove that the material are not cytotoxic and showed acceptable >80% cell viability in all the tested samples. In vivo studies show that both drugs were successful in controlling the implant/tissue interface by suppressing inflammation at the implant site. It was clearly evident that the combined approach of drug loaded carriers along with implanted biosensor shows promise in improving sensor biocompatibility and functionality. Thus, suggesting potential application of alginate microspheres as "smart-tattoo" glucose sensors.
Department of Biosciences and Bioengineering, Indian Institute of Technology, Bombay, Powai, Mumbai 400076, India.
Rahul Dev
RD
Jayant
Michael J
MJ
McShane
Rohit
R
Srivastava
D000464:Alginates / Q000009:adverse effects / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000009:adverse effects / Q000737:chemistry*; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D016903:Drug Monitoring / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects; D020723:Glucuronic Acid / Q000009:adverse effects / Q000737:chemistry; D006603:Hexuronic Acids / Q000009:adverse effects / Q000737:chemistry; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008863:Microspheres; D036103:Nanotechnology / Q000379:methods*; D019736:Prostheses and Implants / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D000464:Alginates; D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D001786:Blood Glucose; D004337:Drug Carriers; D006603:Hexuronic Acids; D004008:Diclofenac; D003907:Dexamethasone; D020723:Glucuronic Acid