Laboratory for Integrative Multiscale Engineering Materials and Systems, Department of Aerospace Engineering, Indian Institute of Science, Bangalore 560012, India; Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore 560027, India.
Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore 560027, India.
Mater Sci Eng C Mater Biol Appl. 2016 Jun;63:78-87. doi: 10.1016/j.msec.2016.02.062. Epub 2016 Feb 23.
Targeting of superior osteogenic drugs to bone is an ideal approach for treatment of osteoporosis. Here, we investigated the potential of using risedronate/zinc-hydroxyapatite (ZnHA) nanoparticles based formulation in a rat model of experimental osteoporosis. Risedronate, a targeting moiety that has a strong affinity for bone, was loaded to ZnHA nanoparticles by adsorption method. Prepared risedronate/ZnHA drug formulation was characterized by field-emission scanning electron microscopy, X-ray diffraction analysis and fourier transform infrared spectroscopy. In vivo performance of the prepared risedronate/ZnHA nanoparticles was tested in an experimental model of postmenopausal osteoporosis. Therapy with risedronate/ZnHA drug formulation prevented increase in serum levels of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b better than risedronate/HA or risedronate. With respect to improvement in the mechanical strength of the femoral mid-shaft and correction of increase in urine calcium and creatinine levels, the therapy with risedronate/ZnHA drug formulation was more effective than risedronate/HA or risedronate therapy. Moreover, risedronate/ZnHA drug therapy preserved the cortical and trabecular bone microarchitecture better than risedronate/HA or risedronate therapy. Furthermore, risedronate/ZnHA drug formulation showed higher values of calcium/phosphorous ratio and zinc content. The results strongly implicate that risedronate/ZnHA drug formulation has a therapeutic advantage over risedronate or risedronate/HA therapy for the treatment of osteoporosis.
将具有成骨作用的药物靶向递送到骨是治疗骨质疏松症的理想方法。在这里,我们研究了使用利塞膦酸钠/锌羟基磷灰石(ZnHA)纳米粒子制剂在实验性骨质疏松症大鼠模型中的潜力。利塞膦酸钠是一种具有强烈骨亲和力的靶向部分,通过吸附法被负载到 ZnHA 纳米粒子上。通过场发射扫描电子显微镜、X 射线衍射分析和傅里叶变换红外光谱对制备的利塞膦酸钠/ZnHA 药物制剂进行了表征。在绝经后骨质疏松症的实验模型中测试了制备的利塞膦酸钠/ZnHA 纳米粒子的体内性能。与利塞膦酸钠/HA 或利塞膦酸钠相比,利塞膦酸钠/ZnHA 药物制剂治疗可更好地预防血清骨特异性碱性磷酸酶和抗酒石酸酸性磷酸酶 5b 水平的升高。就股骨中段机械强度的提高和尿钙、肌酐水平升高的纠正而言,利塞膦酸钠/ZnHA 药物制剂治疗比利塞膦酸钠/HA 或利塞膦酸钠治疗更有效。此外,利塞膦酸钠/ZnHA 药物治疗比利塞膦酸钠/HA 或利塞膦酸钠治疗更能保留皮质骨和小梁骨的微观结构。此外,利塞膦酸钠/ZnHA 药物制剂具有更高的钙/磷比和锌含量。这些结果强烈暗示,与利塞膦酸钠或利塞膦酸钠/HA 治疗相比,利塞膦酸钠/ZnHA 药物制剂在治疗骨质疏松症方面具有治疗优势。