Font Size: a A A

Study On A Drug Release Test Of Zoledronic Acid-loaded Calcium Sulfate In Vitro

Posted on:2015-04-08Degree:MasterType:Thesis
Country:ChinaCandidate:P F ZhangFull Text:PDF
GTID:2284330431492227Subject:Orthopedics
Abstract/Summary:PDF Full Text Request
BackgroudGiant cell-rich lesions of bone is characterized by the presence of numerousmultinucleated osteoclast-type giant cells. These cells have reactive processes andlocally aggressive.They are present in a variety of benign and malignant bone lesions,such as brown tumor of hyperparathyroidism (Recklinghausen disease), giant cellreparative granuloma, aneurismal bone cyst (ABC), chondroblastoma, giant cellosteosarcoma, and malignant and benign giant cell tumor (GCT) of bone. GCT is oneof most common primary bone tumors in clinical which is composed ofmultinucleated giant cells and mononuclear stromal cells. The World HealthOrganization(WHO)defined it as “a kind of potential invasive malignant lesion”.Theincidence of GCT in China is higher than western countries, accounting for14%~16%of the bone tumor. GCT of bone typically presents in persons aged20to40years, which causes the waste of labor resources largely in young adults.GCT ismost commonly found in the long bone, that is distal femur and proximal tibia. It canalso be found in other parts, such as the distal radius, fibula capitulum, proximalfemur, proximal humerus, spine, pelvis, chest and rib cage, skull and feet bone etc.The treatment principle of GCT is cure and control local lesion, save the function ofthe limb. A few decades ago, wide resection is a common procedure and the rate of recurrence is low. However, wide resection might damage joint surface, thereconstruction followed by is also more complex. There are also many seriouscomplications, such as osteoarthritis, etc. In recent years, the common treatment ofgiant cell tumor is intralesional curettage, but simple use this method is difficult toeradicate tumor cell. Little of tumor cells hidden inside the bursa can result in localrecurrence and metastasis of the GCT. Some adjuvant treatment measures are used todeal with tumor cavity to assure kill bone tumors, such as liquid nitrogen, alcohol,phenol, hydrogen peroxide, bone cement, high-speed burr and so on. Adjuvanttreatment of the lesions is approximately like wide resection to achieve excision area,which does not damage the structure of surrounding bone and tissue. It can reduce therecurrence of tumor, at the time can save the limb function greatly. However, none ofthese adjuvant treatment effects has achieved full affirmation and unity at present.Nowadays the bisphosphonate drugs is widely used for lytic bone diseasebecause of its anti-osteoclasts effect. Bisphosphonate drugs is one kind of syntheticpyrophosphate analogues, which is easily absorbed by bone, but it cannot bemetabolism in the human body. It can not only inhibit osteoclast formation, but alsopromote GCT cell apoptosis and inhibit bone resorption, which can inducemesenchymal cells apoptosis in tumors. Biphosphate can play a regulation in bothosteoclasts and osteoblasts. Bisphosphonate drugs can induce multinucleated giantcells of GCT and mononuclear cells of GCT apoptosis, which inhibits the activity ofosteoclasts. In recent years, these drugs have been used in the treatment of bonetumor which associates with osteoclasts mediated soluble bony lesions, such as giantcell tumors of bone, solvent osseous bone metastases, multiple myeloma,osteosarcoma and so on. On the other hand, it can pay an vital role in the preventionof the local recurrence of giant cell tumor afer intralesional curettage. Bisphosphonatedrugs have been developed three generations so far, the representative drug of thethird generation is zoledronic acid, alendronate acid sodium and so on. Intravenousdrip or oral bisphosphonate drugs may have some side effect, such as influenza-likesyndrome, osteonecrosis of the jaw and so on. It can also affect the digestive system,nervous system and skeletal muscle system. The third bisphosphonate drugs isexcreted mainly through kidney without metabolism in human body, which causes a certain amount of waste for the drugs. If zoledronic acid can release slow at locallesions, it could reduce the side effects and can improve the bioavailability of drugs.ObjectiveTo observe a drug delivery system based on calcium sulfate with the differentconcentration of zoledronic acid in vitro.MethodsFive concentrations of zoledronic acid were mixed with calcium sulfate andplaced in distilled water. Then the setting time of two mixed models was recorded.The concentration in the water was measured daily for21days, then use the highperformance liquid chromatography(HPLC) to observe the model of zoledronicrelease at different time.ResultsWithout using drying and strengthening coagulation means, such as aircirculation, the solidification time of group A to E is10.6minutes,20.9minutes,32.8minutes,45.5minutes,58.2minutes with statistically significant (P <0.05). Thecumulative release of B to E is19.11%、23.45%、35.93%、26.88%.The release ofzoledronic acid was greastest during the first24hours for all concentrations anddecreased rapidly during next48hours. The dissolution curve of the over drug-loadedgroups, that is group D and E, waved seriously after48hours.ConclusionThe structure of calcium sulfate was unstable with the increase of loading durgs.Calcium sulfate is a good slow-release carrier of zoledronic within its largest drugloading.Zoledronic can release from calcium sulfate slowly and steadily....
Keywords/Search Tags:calcium sulfate, zoledronic, drug release
PDF Full Text Request
Related items