Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Area of Science:

• Biomaterials Science
• Immunology
• Drug Delivery

Background:

• Lipid mediators like prostaglandin D2 (PGD2) are crucial for host defense but suffer from poor solubility and instability.
• Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) offer a platform to stabilize biomolecules and control their release.
• Developing stable, effective delivery systems for lipid mediators is essential for therapeutic applications.

Purpose of the Study:

• To develop and characterize PGD2-loaded PLGA microspheres (PGD2-MS) for enhanced macrophage activation.
• To evaluate the in vitro efficacy of PGD2-MS in stimulating immune responses in alveolar macrophages (AMs).
• To assess the potential of PGD2-MS as a therapeutic strategy for immunocompromised individuals.

Main Methods:

• PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation technique.
• Characterization included size, zeta potential, surface morphology, and encapsulation efficiency.
• In vitro assays measured phagocytic index, NF-κB activation, nitric oxide, and cytokine production by AMs.

Main Results:

• PGD2-MS were spherical (5.0±3.3 μm) with a zeta potential of -13.4±5.6 mV and 36% encapsulation efficiency.
• PGD2-MS demonstrated higher internalization by AMs and greater NF-κB activation compared to free PGD2.
• PGD2-MS significantly enhanced nitric oxide, TNF-α, IL-1β, and TGF-β production, and modulated responses in LPS-pre-treated AMs.

Conclusions:

• Microencapsulation of PGD2 in PLGA microspheres enhances its biological activity and efficacy in activating macrophages.
• PGD2-MS possess favorable characteristics for interaction with and activation of phagocytic cells.
• PGD2-MS represent a promising strategy for therapeutic interventions in pulmonary immune compromise.