Self-Assembling Peptide as a Potential Carrier for Hydrophobic Anticancer Drug Ellipticine: Complexation, Release and In Vitro Delivery

被引:81
作者
Fung, Shan Yu [1 ]
Yang, Hong [1 ]
Bhola, Priya T. [2 ]
Sadatmousavi, Parisa [1 ]
Muzar, Edward [3 ]
Liu, Mingyao [4 ]
Chen, P. [1 ]
机构
[1] Univ Waterloo, Dept Chem Engn, Waterloo, ON N2L 3G1, Canada
[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada
[3] Univ Toronto, Dept Mat Sci & Engn, Toronto, ON M5S 3E4, Canada
[4] Univ Hlth Network Toronto Gen Res Inst, Latner Thorac Surg Res Labs, Toronto, ON M5G 1L7, Canada
基金
加拿大健康研究院; 加拿大自然科学与工程研究理事会;
关键词
COMPLEMENTARY OLIGOPEPTIDE; MACROMOLECULAR DRUGS; PARTICLE-SIZE; CELL-LINE; NANOPARTICLES; SURFACE; TUMOR; THERAPY; AGENT;
D O I
10.1002/adfm.200800860
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The self assembling peptide EAK16-II is capable of stabilizing hydrophobic compounds to form microcrystal suspensions in aqueous solution. Here, the ability of this peptide to stabilize the hydrophobic anticancer agent ellipticine is investigated. The formation of peptide-ellipticine suspensions is monitored with time until equilibrium is reached. The equilibration time is found to be dependent on the peptide concentration. When the peptide concentration is close to its critical aggregation concentration, the equilibration time is minimal at 5 h. With different combinations of EAK16-II and ellipticine concentrations, two molecular states (protonated or cyrstalline) of ellipticine could be stabilized. These different states of ellipticine significantly affect the release kinetics of ellipticine from the peptide-ellipticine complex into the egg phosphatidylcholine vesicles, which are used to mimic cell membranes. The transfer rate of protonated ellipticine from the complex to the vesicles is much faster than that of crystalline ellipticine. This observation may also be related to the size of the resulting complexes as revealed from the scanning electron micrographs. In addition, the complexes with protonated ellipticine are found to have a better anticancer activity against two cancer cell lines, A549 and MCF-7. This work forms the basis for studies of the peptide-ellipticine suspensions in vitro and in vivo leading to future development of self-assembling peptide-based delivery of hydrophobic anticancer drugs.
引用
收藏
页码:74 / 83
页数:10
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