Effect of size on the in vitro / in vivo drug release and degradation of exenatide-loaded PLGA microspheres

The aim of this study was to investigate the effect of particle size on the in vitro/in vivo drug release and degradation of macromolecule-loaded PLGA microspheres. The active pharmaceutical ingredient exenatide was encapsulated into PLGA microspheres with sizes of 3.80 μm and 18.15 μm, and the in vitro/in vivo drug release and degradation kinetics of microspheres were studied. Small microspheres (3.80 μm) exhibited a higher initial drug release followed by a slower long-term drug release rate (Slope4–49day = 0.81) compared with large microspheres (18.15 μm, Slope4–49day = 1.61). The rapid drug release rate of large microspheres from day 4 to day 28 was attributed to the rapid degradation of PLGA in large microspheres in vitro. After subcutaneous injection into rats, small microspheres released 72% of drug after 4-day administration and released the remaining drug completely after 21 days. Large microspheres showed a slower initial drug release followed by a more rapid drug release in comparison with small microspheres. The high burst release of small microspheres may induce side effects while slow release at late stage may be therapeutically ineffective. In conclusion, it was essential to control the fraction of small microspheres in microsphere formulations to obtain desired drug release behavior.