Stromal-Derived Factor-1 Alpha-Loaded PLGA Microspheres for Stem Cell Recruitment

Stromal-derived factor-1 alpha (SDF-1 alpha) is a chemoattractant that has been investigated for treating various diseases, with the goal of recruiting endogenous stem cells to the site of injury. Biodegradable PLGA microspheres were investigated as a means to deliver SDF-1 alpha in a sustained-release manner. We encapsulated SDF-1 alpha into biodegradable poly(lactide-co-glycolide) (PLGA) microspheres using a double-emulsion solvent extraction/evaporation technique. We varied several formulation parameters, characterized the in vitro release profile of SDF-1 alpha and the size and morphology of microspheres, and determined the bioactivity of the released SDF-1 alpha of stimulating migration of mesenchymal stem cells (MSCs). We found that microspheres fabricated using end-capped PLGA, BSA as an excipient, and low solvent volumes yielded a high encapsulation efficiency (> 64%) and released SDF-1 alpha over a > 50-day timeframe. The released SDF-1 alpha was bioactive and caused significant migration of MSCs throughout the duration of release from the microspheres. We have identified several variables that led to successful encapsulation of SDF-1 alpha into PLGA microspheres. We envision that SDF-l alpha-loaded microspheres may serve as injectable sources of sustained-release chemokine for promoting the recruitment of endogenous stem cells to the site of injury.