Yaru Zhang1, Wei He2, Yawei Du2, Ying Du1, Chao Zhao1, Ying Zhang1, Hu Zhang1, Lihong Yin3, Xinsong Li4. 1. School of Public Health, Southeast University, Nanjing 210009, PR China. 2. School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China. 3. School of Public Health, Southeast University, Nanjing 210009, PR China. Electronic address: lhyin@seu.edu.cn. 4. School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China. Electronic address: lixs@seu.edu.cn.
Abstract
OBJECTIVE: The dimeric artesunate phospholipid conjugate (Di-ART-GPC) is a novel amphipathic artemisinin derivative, which can be assembled into liposomes. Di-ART-GPC liposomes were prepared and evaluated as potential anti-inflammatory agents for rheumatic arthritis (RA). METHODS: Di-ART-GPC was assembled into liposomes utilizing thin film dispersion-high pressure homogenization. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and electron cryo microscopy (cryo-EM) were employed to characterize the liposomal size and morphology. The in vitro cytotoxicity of the Di-ART-GPC liposomes was assessed using Cell Counting Kit-8 (CCK8). The anti-inflammatory effects were studied utilizing the inflammatory cell model. Finally, the in vivo efficacy of the Di-ART-GPC-conjugated liposomes was investigated using the arthritis rat model. RESULTS: The particle size of the Di-ART-GPC liposomes decreased to a narrow range of approximately 70 nm following high-pressure homogenization. The in vitro studies revealed low cytotoxicity and good anti-inflammatory effects of the Di-ART-GPC liposomes, which exhibited significantly higher inhibition of the cell secretion of pro-inflammatory cytokines than ART. The in vivo evaluation confirmed that treatment with Di-ART-GPC resulted in a decline in the ankle swelling rate and a low inflammatory response compared with the model control and ART. CONCLUSION: Di-ART-GPC liposomes demonstrate remarkable potential as novel ART-based anti-inflammatory agents for RA.
OBJECTIVE: The dimeric artesunate phospholipid conjugate (Di-ART-GPC) is a novel amphipathic artemisinin derivative, which can be assembled into liposomes. Di-ART-GPC liposomes were prepared and evaluated as potential anti-inflammatory agents for rheumatic arthritis (RA). METHODS:Di-ART-GPC was assembled into liposomes utilizing thin film dispersion-high pressure homogenization. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and electron cryo microscopy (cryo-EM) were employed to characterize the liposomal size and morphology. The in vitro cytotoxicity of the Di-ART-GPC liposomes was assessed using Cell Counting Kit-8 (CCK8). The anti-inflammatory effects were studied utilizing the inflammatory cell model. Finally, the in vivo efficacy of the Di-ART-GPC-conjugated liposomes was investigated using the arthritisrat model. RESULTS: The particle size of the Di-ART-GPC liposomes decreased to a narrow range of approximately 70 nm following high-pressure homogenization. The in vitro studies revealed low cytotoxicity and good anti-inflammatory effects of the Di-ART-GPC liposomes, which exhibited significantly higher inhibition of the cell secretion of pro-inflammatory cytokines than ART. The in vivo evaluation confirmed that treatment with Di-ART-GPC resulted in a decline in the ankle swelling rate and a low inflammatory response compared with the model control and ART. CONCLUSION:Di-ART-GPC liposomes demonstrate remarkable potential as novel ART-based anti-inflammatory agents for RA.