达沙替尼白蛋白胶束的制备与表征
Preparation and characterization of dasatinib albumin micelles
-
摘要: 研究制备一种聚乙二醇和十二醛双修饰的牛血清白蛋白（PEG-DSA），并探讨其作为达沙替尼（dasatinib，DAS）新型高效胶束载体的初步可行性。采用圆二色谱、核磁共振氢谱、元素分析、红外光谱等方法进行材料结构表征，采用单因素考察法进行PEG-DSA/DAS胶束和非PEG化对照胶束DSA/DAS的工艺优化。结果表明，PEG-DSA与DAS质量比为4∶1时可以获得理化性质合适且稳定、载药量高的最优制剂：平均粒径为（37.21 ± 0.21）nm，多分散指数PDI为0.24 ± 0.04，Zeta电位为?（15.68 ± 0.19）mV，载药量（DL）为（10.22 ± 0.34）%，包封率（EE）为（42.73 ± 1.15）%。与文献报道的DAS纳米制剂相比，PEG-DSA/DAS胶束的载药量显著提高，具有进一步开发的潜力。Abstract: In this study, a polyethylene glycol and dodecaldehyde modified bovine serum albumin (PEG-DSA) was developed, and its feasibility as a new high-efficiency micellar carrier for dasatinib (DAS) was explored.Circular dichroism, 1H NMR, elemental analysis, FT-IR and other methods were used to characterize the material structure and the single factor method was used to optimize the process of PEG-DSA/DAS micelles and non-PEGylated control micelles DSA/DAS.The results indicated that the optimal formulation was obtained with a mass ratio of 4∶1 between PEG-DSA and DAS, with average particle size of (37.21 ± 0.21) nm, polydispersion index (PDI) of (0.24 ± 0.04), Zeta potential of ? (15.68 ± 0.19) mV, drug loading (DL) capacity of (10.22 ± 0.34) %, and encapsulation efficiency (EE) of (42.73 ± 1.15) %. Compared with the currently reported nano-formulations of DAS, the drug loading of PEG-DSA/DAS micellar formulations was significantly increased with potential for further development.
-
Keywords:
- dasatinib /
- albumin amphiphilic modification /
- albumin micelle /
- preparation /
- characterization
-
-
[1] . Recent Results Cancer Res，2018，212：29-68. [2] Steinberg M. Dasatinib：a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia［J］. Clin Ther，2007，29（11）：2289-2308. [3] Quintás-Cardama A，Kantarjian H，Ravandi F，et al. Bleeding diathesis in patients with chronic myelogenous leukemia receiving dasatinib therapy［J］. Cancer，2009，115（11）：2482-2490. [4] Yao Q，Choi JH，Dai Z，et al. Improving tumor specificity and anticancer activity of dasatinib by dual-targeted polymeric micelles［J］. ACS Appl Mater Interfaces，2017，9（42）：36642-36654. [5] Sun JJ，Liu YH，Chen YC，et al. Doxorubicin delivered by a redox-responsive dasatinib-containing polymeric prodrug carrier for combination therapy［J］. J Control Release，2017，258：43-55. [6] Sabra SA，Sheweita SA，Haroun M，et al. Magnetically guided self-assembled protein micelles for enhanced delivery of dasatinib to human triple-negative breast cancer cells［J］. J Pharm Sci，2019，108（5）：1713-1725. [7] Malarvizhi GL，Chandran P，Retnakumari AP，et al. A rationally designed photo-chemo core-shell nanomedicine for inhibiting the migration of metastatic breast cancer cells followed by photodynamic killing［J］. Nanomedicine，2014，10（3）：579-587. [8] Yin XQ，Huo MR，Zhou JP，et al. Synthesis，characterization and drug loading capacity of dodecyl serum albumin for insoluble antitumor drugs［J］. J China Pharm Univ（中国药科大学学报），2011，42（4）：319-323. [9] Suk JS，Xu QG，Kim N，et al. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery［J］. Adv Drug Deliv Rev，2016，99（ Pt A ）：28-51.[10] Gong J，Huo MR，Zhou JP，et al. Synthesis，characterization，drug-loading capacity and safety of novel octyl modified serum albumin micelles［J］. Int J Pharm，2009，376（1/2）：161-168. -
期刊类型引用(8)
1. 刘健弘，张欣橦，李颖娴，杨展，符艺，周瑜芳. 药物缓释体系的研究进展. 广东化工. 2024(15): 90-92+45 . 
百度学术
2. 郑丽君，刘玲，张向荣. 脂质体在乳品中的应用. 中国药剂学杂志(网络版). 2023(01): 34-48 . 百度学术
3. 郭文娣，彭玉帅，许卉，陈华. 脂质体制剂制备工艺及质量控制研究进展. 药物分析杂志. 2023(01): 61-69 . 百度学术
4. 柳宇红，姜宇，郝贵周，刘善奎. 挤出法制备卡巴他赛脂质体的工艺优化. 药学研究. 2023(04): 243-246+284 . 百度学术
5. 吴灿，关延彬，贾永艳. 药剂学课程思政探索——以“脂质体”为例. 中国教育技术装备. 2023(18): 72-74 . 百度学术
6. 毛欣亮，邓惠林，张浩，李吉平，蔡德富，樊丽，孙珈，岳丽玲，潘思文，温宪春. 共载紫草素和盐酸阿霉素pH敏感脂质体的制备及理化性质评价. 齐齐哈尔医学院学报. 2023(23): 2201-2207 . 百度学术
7. 蔡成龙，闫雪生，于蓓蓓，孙丹丹. 透明质酸修饰茯苓皮总三萜脂质体制备与表征研究. 辽宁中医药大学学报. 2022(05): 50-55 . 百度学术
8. 张艺，杭太俊，宋敏. 载药脂质体包封率测定方法的研究进展. 中国药科大学学报. 2021(02): 245-252 . 本站查看
其他类型引用(12)
计量
- 文章访问数:
- HTML全文浏览量: 0
- PDF下载量:
- 被引次数: 20
下载:
