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一项利用培养的破骨细胞对鲑鱼降钙素微球抗吸收活性的研究。

A study of the antiresorptive activity of salmon calcitonin microspheres using cultured osteoclastic cells.

作者信息

Dani Bhas A, Raiche Adrian T, Puleo David A, DeLuca Patrick P

机构信息

Inhale Therapeutic Systems, San Carlos, CA 94070, USA.

出版信息

AAPS PharmSciTech. 2002;3(3):E21. doi: 10.1208/pt030321.

Abstract

The purpose of this study was to evaluate salmon calcitonin (sCT) microspheres in vitro for their antiresorptive activity using cultured osteoclastic cells. The antiresorptive activity of sCT-loaded microspheres, prepared from a low molecular weight hydrophilic poly (lactide-co-glycolide) polymer (PLGA), was studied using bone marrow culture cells harvested from juvenile rats and cultured on slices of devitalized bone for up to 4 weeks. The resorptive activity of osteoclastic cells was quantified in terms of number and type of resorption pits and total area of resorption. Microspheres containing 5.1% sCT released 70% peptide in 2 weeks and 88% in 4 weeks. All sCT treatments inhibited total resorptive activity. A dose-dependent decrease in resorption was observed with sCT microspheres at 2 weeks. The high dose (10 mg of microspheres) produced a 99.5% decrease in resorption at 3 weeks, while the low dose (1 mg) produced an 80% reduction. Exposure of cultures to soluble sCT and sCT-loaded microspheres caused a decrease in the number of large pits, which were the predominant type formed in control cultures. Thus, this system could serve as an in vitro method to evaluate the antiresorptive effect of PLGA-sCT microspheres.

摘要

本研究的目的是使用培养的破骨细胞在体外评估鲑鱼降钙素(sCT)微球的抗吸收活性。由低分子量亲水性聚(丙交酯-共-乙交酯)聚合物(PLGA)制备的载sCT微球的抗吸收活性,采用从幼年大鼠采集的骨髓培养细胞并在失活骨切片上培养长达4周的方法进行研究。破骨细胞的吸收活性根据吸收凹坑的数量和类型以及吸收总面积进行定量。含有5.1% sCT的微球在2周内释放70%的肽,在4周内释放88%。所有sCT处理均抑制了总吸收活性。在2周时,观察到sCT微球导致吸收呈剂量依赖性降低。高剂量(10 mg微球)在3周时使吸收降低了99.5%,而低剂量(1 mg)使吸收降低了80%。将培养物暴露于可溶性sCT和载sCT微球会导致大坑数量减少,大坑是对照培养物中形成的主要类型。因此,该系统可作为一种体外方法来评估PLGA-sCT微球的抗吸收效果。

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