Adah Felix, Benghuzzi Hamed, Tucci Michelle, Russell George, England Barry
University of Mississippi Medical Center, Jackson, MS, USA.
Biomed Sci Instrum. 2007;43:95-103.
This study investigated the effects of dual delivery of statin and vancomycin on the healing process of a femoral defect injury using tricalcium phosphate lysine (TCPL) delivery system in an animal model. The experimental design consisted of 14 rats divided into the following three groups: Group I animals (n=5) served as the intact control without treatment. Group II animals (n=5) were subjected to a surgically induced defect (2 mm, midshaft of the right femur) and implanted (IM) with TCPL capsules loaded with vancomycin (20mg) (TCPL-AB). Group III animals (n=4) were operated on in a similar fashion as Group II, and subsequently implanted with TCPL capsules loaded vancomycin (20 mg) plus statin (5 mg). The animals were euthanized at 30 days post-implantation using overdose of isoflourane. The right femurs were then harvested in addition to the vital organs, the reproductive organs, and sample of the adjacent skeletal muscles. The hard and soft tissues were evaluated histopathologically by following laboratory standard techniques. The results of this study indicated that statin plus vancomycin treated animals healed in a greater magnitude than the sham group (independent evaluators (p<0.001)). Histomorphometric analysis demonstrated that exposure to sustained delivery of statin resulted in increased in cortical width compared to the sham and control groups (p<0.05). Furthermore, the periosteal area was significantly greater than the areas observed in sham group (p<0.05). Image analysis revealed that there were more bone formation in the vancomycin and statin exposed animals than the sham. Overall, the use of TCPL system was able to deliver statin in a sustained manner without eliciting any adverse effects on the reproductive, vital organs and the muscles. In conclusion, data obtained from this study demonstrated that sustained delivery of statin resulted in a remarkable increase in osteogenic activity.
本研究在动物模型中，使用磷酸三钙赖氨酸（TCPL）递送系统，研究了他汀类药物和万古霉素联合递送对股骨缺损损伤愈合过程的影响。实验设计包括将14只大鼠分为以下三组：第一组动物（n = 5）作为未接受治疗的完整对照。第二组动物（n = 5）接受手术诱导的缺损（2毫米，右股骨中段），并植入装载万古霉素（20毫克）的TCPL胶囊（TCPL-AB）。第三组动物（n = 4）以与第二组相似的方式进行手术，随后植入装载万古霉素（20毫克）加他汀类药物（5毫克）的TCPL胶囊。在植入后30天，使用过量异氟烷对动物实施安乐死。然后除了重要器官、生殖器官和相邻骨骼肌样本外，还收获了右股骨。通过遵循实验室标准技术对硬组织和软组织进行组织病理学评估。本研究结果表明，与假手术组相比，他汀类药物加万古霉素治疗的动物愈合程度更高（独立评估者，p<0.001）。组织形态计量学分析表明，与假手术组和对照组相比，持续递送他汀类药物导致皮质宽度增加（p<0.05）。此外，骨膜面积显著大于假手术组观察到的面积（p<0.05）。图像分析显示，与假手术组相比，暴露于万古霉素和他汀类药物的动物有更多的骨形成。总体而言，使用TCPL系统能够持续递送他汀类药物，而不会对生殖器官、重要器官和肌肉产生任何不利影响。总之，本研究获得的数据表明，持续递送他汀类药物导致成骨活性显著增加。
