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

• Published in: Pharmaceutical research 2011-10, Vol.28 (10), p.2477-2489
• Main Authors: Cross, Daisy P., Wang, Chun
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biodegradable materials; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chemokine CXCL12 - chemistry; Chemokine CXCL12 - metabolism; Chemokines - metabolism; Delayed-Action Preparations; Emulsion polymerization; Emulsions - chemistry; Excipients - chemistry; Lactic Acid - chemistry; Medical Law; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mice; Microspheres; Particle Size; Pharmaceutical sciences; Pharmacology/Toxicology; Pharmacy; Polyglycolic Acid - chemistry; Polymers - chemistry; Research Paper; Solvents - chemistry; Stem cells; Wound Healing - drug effects
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-011-0474-x

ABSTRACT 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.