唑来膦酸脂质体的制备及对肿瘤细胞的抑制作用
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摘要
目的制备唑来膦酸脂质体并探讨其对多发性骨髓瘤RPMI 8226肿瘤细胞的抑制作用。方法采用薄膜分散法制备唑来膦酸脂质体,采用磺酰罗丹明B(SRB)染色法考察唑来膦酸脂质体对肿瘤细胞的体外抑制作用。结果制备所得唑来膦酸脂质体的平均粒径为179.9 nm,包封率40.22%,载药量3.54%,平均电位-24.3 m V。唑来膦酸针剂与唑来膦酸脂质体对肿瘤细胞均有抑制增殖作用。结论采用薄膜分散法制得的唑来膦酸脂质体具有较好的稳定性,粒径分布均匀,符合制剂学要求。采用脂质体包裹后的唑来膦酸对肿瘤细胞的抑制作用明显强于唑来膦酸针剂。
AIM To prepare zoledronic acid liposomes and study the inhibitory effect of zoledronic acid liposomes on tumor cells. METHODS Zoledronic acid liposomes were prepared by film dispersion method. And sulforhodamine B( SRB) experiment was used to investigate the inhibitory effect on tumor cells in vitro. RESULTS The average particle size of liposomes was 179. 9 nm,encapsulation efficiency was 40. 22% and drug loading was 3.54%. The zeta potential was- 24. 3 m V. Both zoledronic acid injection and zoledronic acid liposomes could inhibit the proliferation of tumor cells. The proliferation of four cells was inhibited by different concentrations of arsenic trioxide. CONCLUSION Zoledronic acid liposomes prepared by film dispersion method show good stability and uniformity of particle distribution which meet pharmaceutical requirement. The inhibitory effect of zoledronic acid liposomes on tumor cells is significantly stronger than that of zoledronic acid injection.
AIM To prepare zoledronic acid liposomes and study the inhibitory effect of zoledronic acid liposomes on tumor cells. METHODS Zoledronic acid liposomes were prepared by film dispersion method. And sulforhodamine B( SRB) experiment was used to investigate the inhibitory effect on tumor cells in vitro. RESULTS The average particle size of liposomes was 179. 9 nm,encapsulation efficiency was 40. 22% and drug loading was 3.54%. The zeta potential was- 24. 3 m V. Both zoledronic acid injection and zoledronic acid liposomes could inhibit the proliferation of tumor cells. The proliferation of four cells was inhibited by different concentrations of arsenic trioxide. CONCLUSION Zoledronic acid liposomes prepared by film dispersion method show good stability and uniformity of particle distribution which meet pharmaceutical requirement. The inhibitory effect of zoledronic acid liposomes on tumor cells is significantly stronger than that of zoledronic acid injection.
引文
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[2]Vincenzi B,Santini D,Dicuonzo G,et al.Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients[J].J Interferon Cytokine Res,2005,25(3):144.
[3]Caraglia M,Marra M,Naviglio S,et al.Zoledronic acid:an unending tale for an antiresorptive agent[J].Expert Opin Pharmacother,2010,11(1):141.
[4]Scheper MA,Badros A,Chaisuparat R,et al.Effect of zoledronic acid on oral broblasts and epithelial cells:a potential mechanism of bisphosphonate-associated osteonecrosis[J].Br J Haematol,2009,144(5):667.
[5]Guenther A,Gordon S,Tiemann M,et al.The bisphosphonate zoledronic acid has antimyeloma activity in vivo by inhibition of protein prenylation[J].Int J Cancer,2010,12 6(1):239.
[6]Ottewell PD,Lefley DV,Cross SS,et al.Sustained inhibition of tumour growth and prolonged survival following sequential administration of doxorubicin and zoledronic acid in a breast cancer model[J].Int J Cancer,2010,126(2):522.
[7]Hirbe AC,Roelofs AJ,Floyd DH,et al.The bisphosphonate zoledronic acid decreases tumor growth in bone in mice with defective osteoclasts[J].Bone,2009,44(5):908.
[8]Salzano G,Marra M,Porru M,et al.Self-assembly nanoparticles for the delivery of bisphosphonates into tumors[J].Int J Pharmaceutics,2011,403(1-2):292.
[9]Shmeeda H,Amitay Y,Gorin J,et al.Delivery of zoledronic acid encapsulated in folate-targeted liposome results in potent in vitro cytotoxic activity on tumor cells[J].J Controlled Release,2010,146(1):76.
[10]Salzano G,Marra M,Porru M,et al.Self-assembly nanoparticles for the delivery of bisphosphonates into tumors[J].Int J Pharm,2011,403(1-2):292.
[11]Zwolak P,Manivel JC,Jasinski P,et al.Cytotoxic effect of zoledronic acid-loaded bone cement on giant cell tumor,multiple myeloma,and renal cell carcinoma cell lines[J].J Bone Joint Surg Am,2010,92(1):161.
[12]Coleman RE,Winte MC,Cameron D,et al.The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response:exploratory evidence for direct anti-tumour activity in breast cancer[J].Br J Cancer,2010,102(7):1099.