Vitamin E TPGS prodrug micelles for hydrophilic drug delivery with neuroprotective effects
Vitamin E TPGS prodrug micelles for hydrophilic drug delivery with neuroprotective effects
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DOI：
10.1016/j.ijpharm.2012.08.038
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发表时间：
2012-11-15
影响因子：
5.8
通讯作者：
Feng, Si-Shen
中科院分区：
文献类型：
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作者：
Mi, Yu;Zhao, Jing;Feng, Si-Shen
双乳法是目前最常用的亲水性药物纳米粒制备方法，但其存在载药量低、包封率低等缺点。药物释放可能太快，无法持续化疗。本研究以顺铂为模型药物，构建了一种D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）前药胶束体系。我们证明，这样的系统可以成功地提供模型亲水性药物的低临界胶束浓度（CMC）仅为5.01 mg/L，高载药量为4.95%（w/w）和pH响应的药物释放动力学和更高的细胞摄取相比，原始药物和TPGS-cisplatin前药本身。细胞活力实验显示顺铂化疗的显著增强，这通过与HepG 2肝癌细胞培养24、48、72 h后TPGS前药胶束制剂的IC 50值分别从顺铂的3.95、0.98、0.19降低至1.36、0.51、0.08 μ g/mL来证明。此外，这种TPGS前药胶束制剂显示出对顺铂化疗的显著神经保护作用，这通过顺铂和TPGS前药胶束制剂之间对SH-SY 5 Y成神经细胞样细胞的IC 50值的极大增加来证明。TPGS前药胶束也可推广成为一种新的亲水性和疏水性药物和/或成像剂的共递送策略。(C)2012爱思唯尔有限公司版权所有。
Double emulsion has been used most often in formulation of hydrophilic drugs by nanoparticles of biodegradable polymers, which has disadvantages such as low drug loading and low drug encapsulation efficiency due to the drug loss in the process. The drug release may be too fast for sustained chemotherapy. We developed in this research a D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) prodrug micelle system with cisplatin as a model hydrophilic drug. We demonstrated that such a system can successfully deliver the model hydrophilic drug with a low critical micelle concentration (CMC) of only 5.01 mg/L, a high drug load of 4.95% (w/w) and a pH-responsive drug release kinetics and higher cellular uptake in comparison with the original drug and the TPGS-cisplatin prodrug itself. The cell viability experiment showed great enhancement of the cisplatin chemotherapy, which is demonstrated by the IC50 value reduced from 3.95, 0.98, 0.19 for cisplatin to 1.36, 0.51, 0.08 mu g/mL for the TPGS prodrug micelle formulation after 24, 48, 72 h culture with the HepG2 hepatocarcinoma cells, respectively. Furthermore, such a TPGS prodrug micellar formulation showed significant neuroprotective effects for the cisplatin chemotherapy, which is demonstrated by the greatly increased IC50 value for the SH-SY5Y neuroblast-like cells in comparison between cisplatin and the TPGS prodrug micelle formulation. The TPGS prodrug micelles can also be generalized to become a new strategy for codelivery of hydrophilic and hydrophobic drugs and/or imaging agents. (C) 2012 Elsevier B.V. All rights reserved.