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Administration of raloxifene hydrochloride nanosuspensions partially attenuates bone loss in ovariectomized mice

机译:盐酸雷洛昔芬纳米杆菌的施用部分衰减卵巢切除小鼠的骨质损失

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摘要

Postmenopausal osteoporosis is a systemic skeletal disease of fragility fractures due to the loss of the mass and the deterioration of the microarchitecture of bone. This study aimed to assess the effects of raloxifene hydrochloride nanosuspensions (RLX-NSps) on ovariectomized (OVX)-induced osteoporotic rats, and the underlying mechanisms were also investigated in vivo and ex vivo. RLX-NSps were successfully prepared, and the obtained RLX-NSps had a mean particle size of (91.17 +/- 0.73) nm, PDI value of 0.201 +/- 0.03 and zeta potential of (36.3 +/- 1.8) mV. RLX-NSps showed a clear colloidal solution with light yellow opalescence. RLX-NSps were stable in artificial intestinal fluid, artificial gastric fluid, PBS, isotonic glucose and physiological saline. The OVX mice were administered an RLX-NSps or RLX solution for 3 weeks. The bone micro-tomographic histomorphometry and bone mineral density (BMD) were assessed by micro-CT, and the biochemical markers procollagen type I N-terminal propeptide (P1NP) and beta-isomerized C-telopeptide (-CTX) were determined from serum. Finally, primary bone marrow stromal cells (BMSCs) were isolated from the tibia and cultured to evaluate cell proliferation and osteogenic differentiation. The results demonstrated that the RLX-NSp group had a better effect on the bone microarchitecture than the RLX solution group. Therefore, RLX-NSps could partially attenuate bone loss more effectively than RLX solution in OVX mice by inhibiting bone resorption and improving the ability of BMSCs to proliferate and their osteogenic differentiation to some extent. Based on these results, nanosuspensions (NSps) may be a promising delivery system for postmenopausal osteoporosis therapy.
机译:绝经后骨质疏松症是由于损失和骨骼微体系结构的损失而导致的脆弱性骨折的全身骨骼疾病。本研究旨在评估盐酸罗昔芬盐酸盐纳米粒子(RLX-NSP)对卵巢切除(OVX)引起的骨质疏松大鼠的影响,并且还在体内和离体中研究了下面的机制。成功制备了RLX-NSP,所获得的RLX-NSP具有(91.17 +/- 0.73)NM,PDI值为0.201 +/- 0.03和Zeta电位(36.3 +/- 1.8)mV的平均粒度。 RLX-NSP呈现出透明的胶体溶液,具有浅黄色乳白色。 RLX-NSP在人造肠道流体,人造胃液,PBS,等渗葡萄糖和生理盐水中稳定。将OVX小鼠施用RLX-NSP或RLX溶液3周。通过Micro-CT评估骨微突出的组织形态和骨密度(BMD),并从血清中测定生物化学标记型I N-末端肽(P1NP)和β异构化的C-腹分糖(-CTX)。最后,从胫骨中分离出原发性骨髓基质细胞(BMSC)并培养以评估细胞增殖和骨质发生分化。结果表明,RLX-NSP组对骨骼微体系结构比RLX溶液组更好。因此,RLX-NSP可以通过抑制骨吸收并改善BMSCs在一定程度上增殖的能力和它们的成骨分化的能力来部分地衰减骨质损失。基于这些结果,纳米缺失(NSP)可能是绝经后骨质疏松症治疗的有前途的递送系统。

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  • 来源
    《RSC Advances》 |2018年第42期|共9页
  • 作者单位

    Chinese Acad Med Sci Peking Union Med Coll Inst Med Plant Dev 151 Malianwa North Rd Beijing 100193 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Med Plant Dev 151 Malianwa North Rd Beijing 100193 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Med Plant Dev 151 Malianwa North Rd Beijing 100193 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Med Plant Dev 151 Malianwa North Rd Beijing 100193 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Med Plant Dev 151 Malianwa North Rd Beijing 100193 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Med Plant Dev 151 Malianwa North Rd Beijing 100193 Peoples R China;

    Chinese Acad Med Sci Nat Canc Ctr Natl Clin Res Ctr Canc Canc Hosp Beijing 100021 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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