Stromal-derived factor-1 alpha-loaded PLGA microspheres for stem cell recruitment

Pharm Res. 2011 Oct;28(10):2477-89. doi: 10.1007/s11095-011-0474-x. Epub 2011 May 26.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chemokine CXCL12 / chemistry*
  • Chemokine CXCL12 / metabolism
  • Chemokines / metabolism
  • Delayed-Action Preparations
  • Emulsions / chemistry
  • Excipients / chemistry
  • Lactic Acid / chemistry*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects*
  • Mice
  • Microspheres*
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry
  • Solvents / chemistry
  • Wound Healing / drug effects

Substances

  • Chemokine CXCL12
  • Chemokines
  • Cxcl12 protein, mouse
  • Delayed-Action Preparations
  • Emulsions
  • Excipients
  • Polymers
  • Solvents
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid