载舒尼替尼栓塞微球的制备及体外性质研究

doi:10.5246/jcps.2014.08.072

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (8): 558-564.DOI: 10.5246/jcps.2014.08.072

载舒尼替尼栓塞微球的制备及体外性质研究

赵子明, 李佳林, 杨勇杰, 崔代超, 卢晓静, 范田园^*

北京大学药学院药剂学系天然药物及仿生药物国家重点实验室, 北京 100191

收稿日期:2013-11-06 修回日期:2013-11-25 出版日期:2014-08-31 发布日期:2013-12-06
通讯作者: Tel.: 86-10-82805123
基金资助:
State Key Projects (Grant No. 2009ZX09310-001).

Preparation and characterization of sunitinib-loaded microspheres for arterial embolization

Ziming Zhao, Jialin Li, Yongjie Yang, Daichao Cui, Xiaojing Lu, Tianyuan Fan^*

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2013-11-06 Revised:2013-11-25 Online:2014-08-31 Published:2013-12-06
Contact: Tel.: 86-10-82805123
Supported by:
State Key Projects (Grant No. 2009ZX09310-001).

摘要/Abstract

摘要：

近年来载药微球在栓塞治疗中引起了广泛关注。本研究采用反相悬浮聚合法制备了用于栓塞的聚乙烯醇/丙烯酸微球, 首先筛分出粒径在100-1000 μm范围的微球, 并以舒尼替尼为模型药物, 根据离子交换原理制备出载药微球; 系统地评价了空白微球(B-Ms)和载药微球(SU-Ms)的理化性质: 微球的形态、粒径及其分布、平衡含水量、弹性性质等, 考察了微球的载药和体外释药的规律。结果显示: 微球外观圆整, 载药前后微球的粒径均适用于栓塞, 载药后微球平衡含水量下降, 刚性增加, 载药前后微球的弹性均适于栓塞; 微球载药量和包封率主要受药液浓度的影响, 载药微球在磷酸盐缓冲液(PBS)中缓慢释药, 因此, 舒尼替尼载药微球具有动脉栓塞治疗的潜在应用价值。

关键词: 微球, 栓塞, 舒尼替尼, 缓释

Abstract:

Drug-loaded microspheres have been caused much attention in embotherapy in recent years. In this study, polyvinyl alcohol/acrylic acid microspheres were prepared by inverse suspension polymerization method. Sunitinib malate (SU) was used as a model drug and loaded on microspheres through ion-exchange mechanism. We investigated the characterization of blank microspheres (B-Ms) and sunitinib-loaded microspheres (SU-Ms) in vitro, including morphology, size distribution, equilibrium water content (EWC), elasticity, drug loading and drug release. The result showed that both B-Ms and SU-Ms were spherical withsmooth surface. The particle size of B-Ms and SU-Ms were both suitable for embolization. Compared with that of B-Ms, the EWC of SU-Ms was decreased and the rigidity of SU-Ms was increased. Drug loading and entrapment efficiency ofmicrospheres were mainly affected by the concentration of sunitinib solution than by the size of microspheres. SU-Ms exhibited a sustained release in phosphate buffer solution (PBS). Thus, the SU-Ms may have potential application for arterial embolization.

Key words: Microspheres, Embolization, Sunitinib, Sustained release

中图分类号:

R943

Supporting:

赵子明, 李佳林, 杨勇杰, 崔代超, 卢晓静, 范田园. 载舒尼替尼栓塞微球的制备及体外性质研究[J]. 中国药学(英文版), 2014, 23(8): 558-564.

Ziming Zhao, Jialin Li, Yongjie Yang, Daichao Cui, Xiaojing Lu, Tianyuan Fan. Preparation and characterization of sunitinib-loaded microspheres for arterial embolization[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(8): 558-564.

参考文献

[1] Corr, P.D. Cardiovasc. Intervent. Radiol. 2005, 28,439-441.

[2] Osuga, K.; Hori, S.; Kitayoshi, H.; Khankan, A.A.; Okada, A.; Sugiura, T.; Murakami, T.; Hosokawa, K.; Nakamura, H. J. Vasc. Interv. Radiol. 2002,13, 1125-1133.

[3] Siskin, G.P.; Beck, A.; Schuster, M.; Mandato, K.; Meridith, E.; Herr, A. J. Vasc. Interv. Radiol. 2008,19,58-65.

[4] Spies, J.B.; Allison, S.; Flick, P.; McCullough, M.; Sterbis, K.; Cramp, M.; Bruno, J.; Jha, R. J. Vasc. Interv. Radiol. 2004,15, 793-800.

[5] Tasar, M.; Gulec, B.; Bozlar, U.; Saglam, M.; Ugurel, M.S.; Ucoz, T. Clin. Imaging. 2005, 29, 325-330.

[6] Lau, W.Y.; Yu, S.C.; Lai, E.C.; Leung, T.W. J. Am. Coll. Surg. 2006, 202, 155-168.

[7] De Gregorio, M.A.; Medrano, J.; Mainar, A.; Alfonso, E.R.; Rengel, M. Arch. Bronconeumol. 2006, 42, 49-56.

[8] Treska, V.; Skalický, T.; Sutnar, A.; Liska, V.; Ferda, J.; Mírka, H.; Slauf, F.; Duras, P.; Kreuzberg, B. Rozhl. Chir. 2010, 89, 456-460.

[9] Skalicky, T.; Treska, V.; Sutnar, A.; Liska, V.; Duras, P.; Slauf, F. Bratisl. Lek. Listy. 2010, 111, 676-679.

[10] Varela, M.; Real, M.I.; Burrel, M.; Forner, A.; Sala, M.; Brunet, M.; Ayuso, C.; Castells, L.; Montañá, X.; Llovet, J.M.; Bruix, J. J. Hepatol. 2007, 46, 474-481.

[11] Taylor, R.R.; Tang, Y.; Gonzalez, M.V.; Stratford, P.W.; Lewis, A.L. Eur. J. Pharm. Sci. 2007, 30, 7-14.

[12] Liapi, E.; Lee, K.H.; Georgiades, C.C.; Hong, K.; Geschwind, J.F. Tech. Vasc. Interv. Radiol. 2007, 10, 261-269.

[13] Wang, C.; Liu, J.; Gao, Q.; Bi, Y.; Gan, L.; Wang, X.; Hou, S. Int. J. Pharm. 2007, 336, 361-366.

[14] Jordan, O.; Denys, A.; De Baere, T.; Boulens, N.; Doelker, E. J. Vasc. Interv. Radiol. 2010, 21, 1084-1090.

[15] Arora, A.; Scholar, E.M. J. Pharmacol. Exp. Ther. 2005, 315, 971-979.

[16] General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China (AQSIQ); Standaraization Adminstration of the People’s Republic of China. 2008. This article can be found online at http://www.bzwxw.com/html/19/2382.html.

[17] Hidaka, K.; Moine, L.; Collin, G.; Labarre, D.; Grossiord, G.L.; Huang, N.; Osuga, K.; Wadab, S.; Laurentf, A. J. Mech. Behav. Biomed. 2011, 4, 2161-2167.

[18] Laurent, A.; Wassef, M.; Saint Maurice, J.P.; Namur, J.; Pelage, J.P.; Seron, A.; Chapot, R.; Merland, J.J. Invest. Radiol.2006, 41, 8-14.

[19] Lewis, A.L.; Gonzalez, M.V.; Lloyd, A.W.; Hall, B.; Tang, Y.; Willis, S.L.; Leppard, S.W.; Wolfenden, L.C.; Palmer, R.R.; Stratford, P.W. J. Vasc. Interv. Radiol. 2006,17, 335-342.

[20] Zhou, C.; Cui, D.; Zhang, Y.; Yuan, H.; Fan, T. J. Mater. Sci. Mater. Med. 2012, 23, 409-418.

[21] Cui, D.C.; Lu, W.L.; Sa, E.A.; Gu, M.J.; Lu, X.J.; Fan, T.Y. Int. J. Pharm.2012, 436, 527-535.

[22] Borovac, T.; Pelage, J.P.; Kasselouri, A.; Prognon, P.; Guiffant, G.; Laurent, A. J. Control. Release. 2006, 115, 266-274.

[23] Abdekhodaie, M.J.; Wu, X.Y. Biomaterials. 2006, 27, 3652-3662.

载舒尼替尼栓塞微球的制备及体外性质研究

Preparation and characterization of sunitinib-loaded microspheres for arterial embolization

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