Hemolytic Assessment of Geranylgeraniol/Clindamycin-Loaded Composite Hydrogel

Abstract

Objectives: This study investigated the hemolytic activity of a geranylgeraniol (GGOH)/ clindamycin (CDM)-loaded composite hydrogel developed as a potential preventive measure for medication-related osteonecrosis of the jaw associated with bisphosphonate (MRONJ-B). Methods: The surface and structural properties of the drug-loaded hydrogel were char-acterized using stereomicroscopy, scanning electron microscopy, confocal fluorescence microscopy, and micro-computed tomography. The hemolytic activity of the drug-free (control) and drug-loaded hydrogels was comparatively assessed using three in vitro models: washed red blood cells (RBCs), diluted whole blood, and clotted whole blood, to evaluate the impact of the plasma and fibrin matrix on the hemolytic potential of the materials. Results: The results showed that the drug-loaded hydrogel exhibited an average pore size of 38±24 μm, with a porosity of 84±4.3% and an interconnectivity of 99.9±0.1%. The control hydrogel demonstrated minimal hemolysis (<0.5%) in all test models. While the drug-loaded hydrogel exhibited increased hemolysis (>5%) in both washed RBC and diluted whole blood models, the presence of natural fibrin formation and platelet lysate significantly mitigated the hydrogel's hemolytic activity. Notably, platelet lysate encap-sulation provided superior RBC protection compared to natural fibrin within the clotted whole blood model. Histological analysis of the drug-loaded hydrogel in ex vivo cultures with clotted whole blood did not reveal significant RBC toxicity. Conclusions: These findings suggested that the drug-loaded composite hydrogel may be suitable for further in vivo investigations of its biocompatibility and efficacy in preventing MRONJ-B.