Related Experiment Videos
In vitro phagocytosis and monocyte-macrophage activation with poly(lactide) and poly(lactide-co-glycolide)
Sandra Prior1, Bruno Gander, Natalia Blarer
1Department of Microbiology, University of Navarra, Apdo. 177, 31080 Pamplona, Navarra, Spain.
Abstract:
Treatment of many intracellular infections in the mononuclear phagocytic system (MPS), requires targeting of antibiotics by a drug delivery system. The objective of this study was to examine whether the particular nature of microspheres, made of end-group capped and uncapped poly(lactide) [PLA] and poly(lactide-co-glycolide) [PLGA 50:50 and PLGA 75:25], affect the uptake into and also the activation of monocyte-macrophages. Placebo and gentamicin sulfate containing microspheres were incubated with J774 murine monocyte-macrophages and fresh human blood monocytes. Phagocytosis became more efficient with increasing polymer hydrophobicity, whereas opsonization of the particles in serum exerted inconsistent effects. Monocyte activation was determined by flow cytometry and measured as oxidative burst. The cellular oxidative burst induced by the particles was higher for end-group uncapped polymers. Opsonization increased significantly the oxidative activity of J774 monocytes, but affected inconsistently that of human blood monocytes. The results demonstrate that PLA and PLGA microspheres loaded with gentamicin sulfate were efficiently phagocytosed in vitro. The end-group uncapped polymer-type microspheres promoted significantly cell activation, which may be of importance for drug delivery and targeting to intracellular infections.
Insights
Drug delivery microspheres made of poly(lactide) and poly(lactide-co-glycolide) show enhanced uptake by immune cells. Uncapped polymers significantly increase cell activation, improving potential for treating intracellular infections.
Area of Science:
- Biomaterials Science
- Immunology
- Drug Delivery Systems
Background:
- Intracellular infections within the mononuclear phagocytic system (MPS) necessitate targeted antibiotic delivery.
- Polymeric microspheres are investigated as a drug delivery system for enhanced therapeutic efficacy.
Purpose of the Study:
- To evaluate how microsphere properties, specifically polymer type (poly(lactide) [PLA] and poly(lactide-co-glycolide) [PLGA]) and end-group capping, influence monocyte-macrophage uptake and activation.
- To assess the impact of gentamicin sulfate-loaded microspheres on immune cell interactions.
Main Methods:
- Incubation of J774 murine monocyte-macrophages and human blood monocytes with placebo and gentamicin sulfate-loaded microspheres composed of varying PLA and PLGA formulations.
- Quantification of phagocytosis efficiency based on polymer hydrophobicity and serum opsonization.
- Measurement of monocyte activation via oxidative burst using flow cytometry.
Main Results:
- Phagocytosis efficiency increased with polymer hydrophobicity; serum opsonization had variable effects.
- End-group uncapped polymers induced a significantly higher oxidative burst (monocyte activation) compared to capped polymers.
- Gentamicin sulfate-loaded PLA and PLGA microspheres demonstrated efficient in vitro phagocytosis.
Conclusions:
- Polymeric microsphere characteristics, including end-group capping and hydrophobicity, significantly impact their interaction with mononuclear phagocytes.
- End-group uncapped microspheres enhance monocyte activation, suggesting improved potential for targeted drug delivery against intracellular pathogens.
- These findings are crucial for optimizing microsphere-based drug delivery systems for intracellular infections.