Curcuminoid (CRE-Ter)/Liposome as delivery platform for anti-osteoclastogenesis via NF-κB/ERK pathways in RANKL-induced RAW 264.7 cells through PLA foams.

Abstract Aims Curcuminoid (CRE-Ter) is the active component of turmeric, and is widely understood to offer anticancer, antioxidant, and anti-inflammatory properties. The drawbacks, however, include rapid metabolism and systemic elimination as well as minimal bioavailability. In an attempt to address the issue of bioavailability, this study seeks to encapsulate CRE-Ter in a liposome before its incorporation on PLA foams in order to inhibit the process of osteoclastogenesis which takes place in RANKL-induced RAW 264.7 cells. Main methods Having encapsulated the CRE-Ter into the liposomes, the influence of the release of liposomal CRE-Ter from PLA foams in order to inhibit the process of osteoclastogenesis in the case of RANKL-induced RAW 264.7 cells was investigated. By measuring the decline in tartrate-resistant acid phosphatase (TRAP) content it was possible to evaluate the influence of CRE-Ter/Liposome upon osteoclastogenesis in vitro. Immunocytochemistry was employed to assess the marker for the monocyte/macrophage cells F4/80 content, while Western blots were used to evaluate the underlying mechanisms involved. Cell migration was assessed using in vitro cells overgrowth assay where the numbers of cells were counted using hematoxylin and eosin staining, and SEM and TEM imaging. Key findings The findings demonstrate a novel method which employs tissue engineering scaffolds, which are produced to work alongside advanced additive manufacturing techniques with their basis in concepts from the field of alternative medicine. Initially, it was confirmed that CRE-Ter/Liposome at 20 μg/ml is able to inhibit the creation of multinucleated osteoclasts which are induced by the receptor activator of the nuclear factor-κB ligand (RANKL) in RAW 264.7 cells. It was shown that the CRE-Ter/liposome was able to increase the F4/80 content (F4/80 immunohistochemistry) in the RANKL treated RAW 264.7 cells. The TRAP content was lowered by the CRE-Ter/liposome along with the osteoclast-specific gene content such as cathepsin K, via the use of liposome-encapsulated PLA foams. When treated with CRE-Ter/liposome, RANKL-induced NF-κB and ERK components such as NF-κB-p65, ERK, phospho-NF-κB-p65, and phospho-ERK pathways were all suppressed. Significance The successful encapsulation of CRE-Ter into the liposomes offered a new opportunity to provide a new inhibitor of osteoclastogenesis and offers the possibility of developing treatments capable of addressing diseases which concern abnormal bone lysis.