Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis

Abstract

Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression.

Alternative Therapeutic Approach for Cartilage Repair

“…This process is a result of osteoclast activation known as osteoclastogenesis [19]. The receptor activator NF-kappa ligand (RANKL) is produced by some cells as the osteoblast and has an affinity for RANK, which is present in the membrane of osteoclast precursor cells [20].…”

“…Moreover, curcumin has been shown to inhibit the activator protein 1 (AP-1) pathway and NF-κB leading to the suppression of the production of MMP-3, MMP-9, and MMP-13 [15,19]. Zhang et al [9] demonstrated in a mouse model that the production of MMP-1, MMP-3, MMP-13, IL-1β,TNF-α, and ADAMTS5 was decreased when the animals were treated with curcumin.…”

“…Zhang et al [9] demonstrated in a mouse model that the production of MMP-1, MMP-3, MMP-13, IL-1β,TNF-α, and ADAMTS5 was decreased when the animals were treated with curcumin. They also showed an increase in the expression of the chondroprotective gene CITED 2 (Cbp/P300 interacting transactivator with Glu/Asp rich carboxy terminal domain 2), which seems to be involved in the suppression of NF-κB activity [9,19]. Curcumin has also been related to the stimulation of the production of type II collagen and glycosaminoglycan by chondrocytes [5].…”

“…Consequently, it inhibits the expression of pro-apoptotic genes in chondrocytes (caspase-3) and the formation of inflammatory mediators [18]. Thus, it is responsible for the downregulation of lipoxygenases, COX-2, phospholipase A2, prostaglandin E2 (PGE2), IL-1β, IL-6, and IL-8 [19,30]. Wherefore, curcumin blocks the signaling by NF-kB, leading to the inhibition of this factor resulting in the decrease of the degradation of collagen.…”

Phytomedicine in Joint Disorders

“…The ability to prevent the destructive changes in joints and periarticular bone seems to be comparable to that of betamethasone [38,39]. Liposomal encapsulation may help overcome the poor bioavailability problem generated by the low water-solubility [40]. The osteoclast-osteoblast balance is tipped in favor of bone building, while halting the OA progression [40].…”