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Stability, Efficacy, and Immunomodulatory Impact of Nanoemulsion-encapsulated Lipoxin A4 in the Context of Pulpal Inflammation

Year: 2026

Type: article

Abstract: INTRODUCTION: Lipoxin A4 (LXA4) is a specialized proresolving mediator with the potential to modulate dental pulp inflammation. However, its therapeutic use is limited by instability and rapid degradation. This study aimed to develop and evaluate LXA4-loaded nanoemulsions (NELX) as a delivery system to promote inflammation resolution both in vitro and in vivo. METHODS: NELX were formulated with LXA4 and characterized by dynamic light scattering, tunable resistive pulse sensing, scanning transmission electron microscopy, and liquid chromatography-tandem mass spectrometry. Encapsulation efficiency, stability, and drug payload were determined. In vitro, THP-1-derived macrophages (M0, M1, and M2) were exposed to NELX, and metabolic activity, cytokine expression, and secretion were assessed. In vivo efficacy was investigated in a murine air pouch model and a rat molar pulpitis model. Histologic and immunohistochemical analyses (hematoxylin and eosin, cluster of differentiation [CD] CD68, and CD163) were performed. RESULTS: NELX achieved complete encapsulation (100%) of 20 μM LXA4 by day 3 and remained stable for 45 days at 4°C. In vitro, NELX preserved metabolic activity and promoted macrophage polarization toward an anti-inflammatory M2 phenotype, with increased interleukin (IL) 10 and IL-1 receptor antagonist expression and IL-1 receptor antagonist secretion. In vivo, NELX reduced IL-6 levels in the air pouch model and suppressed IL-6 and IL-1β secretion in the pulpitis model, with effects comparable to Ledermix Paste. Histology confirmed reduced inflammatory infiltration and enhanced recruitment of CD163+ macrophages. CONCLUSIONS: NELX provide a stable and effective delivery system for LXA4, promoting resolution of dental pulp inflammation through targeted immunomodulation. This strategy holds promise for novel biologically based anti-inflammatory therapies in endodontics.

Source: Journal of Endodontics

DOI: 10.1016/j.joen.2026.08.015