Purpose: Stromal-derived factor-1 alpha (SDF-1α) 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-1α in a sustained-release manner. Methods: We encapsulated SDF-1α 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-1α and the size and morphology of microspheres, and determined the bioactivity of the released SDF-1α of stimulating migration of mesenchymal stem cells (MSCs). Results: 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-1α over a >50-day timeframe. The released SDF-1α was bioactive and caused significant migration of MSCs throughout the duration of release from the microspheres. Conclusions: We have identified several variables that led to successful encapsulation of SDF-1α into PLGA microspheres. We envision that SDF-lα-loaded microspheres may serve as injectable sources of sustained-release chemokine for promoting the recruitment of endogenous stem cells to the site of injury.
Bibliographical noteFunding Information:
This work is supported in part by the University of Minnesota’s Institute for Engineering in Medicine (IEM) and an NIH Biotechnology Training Grant (Grant Number T32 GM008347). Special thanks to Dr. Jianyi Zhang (Department of Medicine, University of Minnesota) for kindly providing the GFP-expressing porcine MSCs. We are also grateful to Dr. Nathan Lockwood for his careful review and critique of the manuscript.
- controlled release