体外冲击波响应型唑来膦酸钙纳米颗粒靶向控释对骨质疏松骨代谢及骨量的影响OA北大核心CSTPCD

Objective To study the preparation of extracorporeal shock wave(ESW)-responsive zoledronic acid(ZOL)calcium nanoparticles[ZOL-Ca nanoparticles(ZCNP)]and their effects of targeted controlled release on bone metabolism and bone mass in osteoporosis.Methods ZCNP was prepared by template method using ZOL as phosphorus source and CaCl2 as calcium source.ZCNP was characterized by scanning electron microscopy and dynamic light scattering.The loading of ZOL as well as the drug loading rate were evaluated by UV-Vis absorption spectroscopy and inductively coupled plasma photoemission spectroscopy.The effects of ZCNP on the cell viability of murine-derived bone marrow mononuclear cells(BMMs)were detected by CCK-8 assay;the biocompatibility of ZCNP was examined by hemolysis assay.The bone targeting of ZCNP was verified by fluorescent labeling.The ESW responsiveness of ZCNP was verified using drug release assay.In vitro,the osteoblastic inhibition of ZCNP was examined using TRAP staining;the effect of ZCNP on osteogenic activity was examined by ARS staining.In vivo,the effect of ZCNP on bone mass was verified using the ovariectomy(OVX)osteoporosis model.Results ZCNP has a spherical structure of about 60 nm,and the ZOL loading rate of ZCNP was(59.68±1.48)％.The effects of ZCNP on the cellular activity of mouse BMMs at the concentrations of 0,0.01,0.1,1,and 10 μmol/L did not show any significant difference(P＞0.05).ZCNP can release ZOL rapidly under the action of ESW.The ESW+ZCNP group inhibited osteoclast(OC)activity and promoted osteoblast(OB)proliferation.The ESW+ZCNP group significantly increased local bone mass in the OVX osteoporosis model.Conclusions ESW-responsive ZCNP can prevent osteoporotic fracture by inhibiting OB and promoting osteogenesis to enhance local bone mass in OVX model through effective and precise targeted controlled release.