Lin Juan, Zhou Qing-Han, Zhao Xiao-Jun
Institute for Nanobiomedical Technology and Membrane Biology, Sichuan University, Chengdu 610041, China.
Guang Pu Xue Yu Guang Pu Fen Xi. 2009 Oct;29(10):2792-7.
Amphiphilic peptide is becoming attractive as a potential drug carrier to improve the dissolvability of hydrophobic drugs in aqueous system thus facilitating the drug undertaken by target cells. Here, we reported the ability of a novel designed self-assembling peptide RGA16 (Ac-RADAGAGARADAGAGS-NH2) in drug encapsulation and transfer into lipid vesicles. Pyrene was used as a model hydrophobic drug, and egg phosphatidylcholine (EPC) vesicles were used as plasma membranes mimic. It was found that the pyrene and peptide formed complex in water with mechanical stirring, and the time duration over which the complex formed was about 5 days. Initial evidence of the association between RGA16 and pyrene was the observation of a clouding phenomenon. Further investigation on the interaction between RGA16 and pyrene was carried out using fluorescence spectra and scanning electron microscopy (SEM). SEM micrographs showed that pyrene crystals and peptide were absorbed by each other and the size of the pyrene-peptide complexes was larger than 10 microm, which provided an evidence for the encapsulation of pyrene molecule by the amphiphilic peptide. The steady-fluorescence excitation profiles showed that the pyrene was presented in the crystalline form when stabilized by RGA16 and molecularly migrated from its peptide coating into the membrane bilayers of EPC vesicles when the suspension was mixed with EPC vesicles. The release behavior of pyrene into EPC vesicles was investigated by steady-fluorescence emission spectra, and a calibration curve for the amount of pyrene released into the EPC vesicles at a given time was used to determine the final concentration of pyrene released into lipid vesicles from peptide-pyrene complex. It was found that the pyrene concentration in EPC vesicles was displayed as a function of time. The data presented in the present work suggested that the novel designed amphiphilic peptide could stabilize the hydropholic drug in aqueous solution and deliver it into the membrane bilayers of EPC vesicles.
两亲性肽作为一种潜在的药物载体正变得具有吸引力,它能提高疏水性药物在水性体系中的溶解性,从而便于靶细胞摄取药物。在此,我们报道了一种新设计的自组装肽RGA16(Ac-RADAGAGARADAGAGS-NH2)在药物包封及向脂质体转移方面的能力。芘被用作模型疏水性药物,而鸡蛋磷脂酰胆碱(EPC)脂质体被用作质膜模拟物。研究发现,芘和肽在机械搅拌下于水中形成复合物,复合物形成的持续时间约为5天。RGA16与芘之间缔合的初步证据是观察到的浑浊现象。利用荧光光谱和扫描电子显微镜(SEM)对RGA16与芘之间的相互作用进行了进一步研究。SEM显微照片显示,芘晶体和肽相互吸附,芘 - 肽复合物的尺寸大于10微米,这为两亲性肽包封芘分子提供了证据。稳态荧光激发图谱表明,芘在被RGA16稳定时呈晶体形式,当悬浮液与EPC脂质体混合时,芘分子从其肽包衣迁移到EPC脂质体的膜双层中。通过稳态荧光发射光谱研究了芘向EPC脂质体中的释放行为,并使用给定时间释放到EPC脂质体中的芘量的校准曲线来确定从肽 - 芘复合物释放到脂质体中的芘的最终浓度。研究发现,EPC脂质体中的芘浓度随时间变化。本研究呈现的数据表明,新设计的两亲性肽能够在水溶液中稳定疏水性药物并将其递送至EPC脂质体的膜双层中。