Exenatide-loaded PLGA microspheres with improved glycemic control: in vitro bioactivity and in vivo pharmacokinetic profiles after subcutaneous administration to SD rats

Peptides. 2013 Aug:46:172-9. doi: 10.1016/j.peptides.2013.06.005. Epub 2013 Jun 14.

Abstract

A subcutaneous exenatide delivery system was developed and characterized in vitro and in vivo. The results clearly showed that the exenatide loaded PLGA microspheres prepared by using a non-aqueous processing medium had low burst release and high drug encapsulation efficiency. Exenatide loaded in the microspheres preserved its bioactivity. The pharmacokinetics parameters were determined after subcutaneous administration of microspheres to SD rats. The plasma concentration of the single dose of the sustained-release microspheres attained C(max) of 108.19±14.92 ng/ml at t(max) of 1.33±0.58 h and the t(½) was 120.65±44.18 h. There was a linear correlation between the in vitro and in vivo release behavior (R²=0.888). Exenatide loaded microspheres may prove to have great potential for clinical use.

Keywords: Exenatide; Glycemic control; PLGA microspheres; Pharmacokinetic profile; Subcutaneous administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Cell Line
  • Delayed-Action Preparations
  • Drug Carriers
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor
  • HEK293 Cells
  • Humans
  • Incretins / blood
  • Incretins / pharmacokinetics*
  • Incretins / pharmacology
  • Lactic Acid
  • Male
  • Microspheres
  • Peptides / blood
  • Peptides / pharmacokinetics*
  • Peptides / pharmacology
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / agonists*
  • Venoms / blood
  • Venoms / pharmacokinetics*
  • Venoms / pharmacology

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Drug Carriers
  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Exenatide