Visual evidence of acidic environment within degrading poly(lactic-co- glycolic acid) (PLGA) microspheres

Karen Fu, Daniel W. Pack, Alexander M. Klibanov, Robert Langer

Research output: Contribution to journalArticlepeer-review

679 Scopus citations


Purpose. In the past decade, biodegradable polymers have become the materials of choice for a variety of biomaterials applications. In particular, poly(lactic-co-glycolic acid) (PLGA) microspheres have been extensively studied for controlled-release drug delivery. However, degradation of the polymer generates acidic monomers, and acidification of the inner polymer environment is a central issue in the development of these devices for drug delivery. Methods. To quantitatively determine the intrapolymer acidity, we entrapped pH-sensitive fluorescent dyes (conjugated to 10,000 Da dextrans) within the microspheres and imaged them with confocal fluorescence microscopy. The technique allows visualization of the spatial and temporal distribution of pH within the degrading microspheres (1). Results. Our experiments show the formation of a very acidic environment within the particles with the minimum pH as low as 1.5. Conclusions. The images show a pH gradient, with the most acidic environment at the center of the spheres and higher pH near the edges, which is characteristic of diffusion-controlled release of the acidic degradation products.

Original languageEnglish
Pages (from-to)100-106
Number of pages7
JournalPharmaceutical Research
Issue number1
StatePublished - 2000

Bibliographical note

Funding Information:
We would like to thank Michael Frongillo of the MIT microscopy center for his expertise on the SEM, and Maria Figueiredo of Alkermes, Inc. for providing PVA-free microspheres made with the spray/freeze-drying technique. This work was supported in part by NIH grant GM26698 and by the Biotechnology Process Engineering Center at MIT.


  • Confocal fluorescence microscopy
  • PH
  • PLGA microspheres
  • Protein drug delivery

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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