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Updated: Jul 28, 2026
Study of Phagolysosome Biogenesis in Live Macrophages
Published on: March 10, 2014
Raman imaging of PLGA microsphere degradation inside macrophages
Aart A van Apeldoorn1, Henk-Jan van Manen, Jeroen M Bezemer
1Polymer Chemistry and Biomaterials Group, Biomedical Technology Institute, University of Twente, Bilthoven, The Netherlands. a.a.vanapeldoorn@tnw.utwente.nl
Abstract:
Understanding the degradation behavior of polymeric microspheres is crucial for the successful application of such devices in controlled drug delivery. The degradation mechanism of poly(lactic-co-glycolic acid) (PLGA) microspheres inside phagocytic cells is not known, but different models for degradation in aqueous solution have been proposed. We have used confocal Raman spectroscopy and imaging to study the intracellular degradation of PLGA microspheres inside individual macrophages. Our results show that ingested microspheres degrade in a heterogeneous manner, with a more rapid degradation in the center. Comparison of Raman spectra from degrading beads with those of uningested beads reveals that ester hydrolysis occurs throughout the phagocytosed microspheres, with a selective loss of glycolic acid units. Furthermore, we show that PLGA degradation is a cell-mediated process, possibly caused by the low pH of the phagosome and/or the presence of hydrolytic enzymes. In conclusion, we have demonstrated that the chemical composition of degrading polymers inside cells can be probed by Raman spectral imaging. This technique will expand the capabilities of investigating biomaterial degradation in vivo.
Insights
Polymeric microsphere degradation inside cells was studied using Raman spectroscopy. Ingested poly(lactic-co-glycolic acid) microspheres degraded heterogeneously, indicating a cell-mediated process crucial for drug delivery.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Cell Biology
Background:
- Controlled drug delivery relies on understanding polymeric microsphere degradation.
- The intracellular degradation mechanism of poly(lactic-co-glycolic acid) (PLGA) microspheres remains largely unknown.
- Existing models primarily focus on degradation in aqueous solutions.
Purpose of the Study:
- To investigate the intracellular degradation of PLGA microspheres within phagocytic cells.
- To elucidate the degradation mechanism and chemical changes occurring inside macrophages.
- To assess the utility of confocal Raman spectroscopy for probing in vivo biomaterial degradation.
Main Methods:
- Confocal Raman spectroscopy and imaging were employed.
- PLGA microspheres were ingested by individual macrophages.
- Raman spectra of ingested and uningested microspheres were compared.
Main Results:
- PLGA microspheres exhibited heterogeneous intracellular degradation, faster at the core.
- Ester hydrolysis was observed throughout the microspheres.
- A selective loss of glycolic acid units was detected.
- PLGA degradation was identified as a cell-mediated process, influenced by phagosomal pH and/or enzymes.
Conclusions:
- Confocal Raman spectral imaging can effectively probe the chemical composition of degrading polymers within cells.
- This technique offers expanded capabilities for investigating biomaterial degradation in vivo.
- Understanding cell-mediated degradation is vital for optimizing PLGA-based drug delivery systems.
