Won Sang Ho, Lee Jong Uk, Sim Sang Jun
School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Korea.
J Nanosci Nanotechnol. 2013 Jun;13(6):3792-800. doi: 10.1166/jnn.2013.7205.
A crucial issue for current liposomal carriers in clinical applications is the sustained-release property of the encapsulated drugs. We have developed novel fluorogenic pH-sensitive polymerized liposomes composed of polydiacetylene (PDA) lipids and other types of lipids. Unilamellar liposomes containing 10,12-pentacosadiynoic acid (PCDA), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and N-palmitoyl homocysteine (PHC) were loaded with ampicillin. These liposomes fused to each other rapidly when the medium pH was lowered from 7 to 4. The polymerized liposomes were characterized in terms of particle size distribution. The liposome size increased approximately 20-fold from 110.0 +/- 19.3 nm to 2046.7 +/- 487.4 nm as the pH was lowered. Cross-linking of the diacetylene lipids prevents drug leakage and the encapsulated drug can be instantaneously released at acidic pH condition. The ampicillin was nearly completely released (74.4 +/- 3.9%) from liposomes within 4 h under acidic pH conditions and the released amounts of ampicillin were analyzed by HPLC. Finally, the therapeutic effect was observed by the appearance of plaques on a lawn of E. coli, and fluorescent images of the PDA liposomes were taken from the plaques for drug release monitoring. As a result, this research demonstrates that such novel pH-sensitive polymerized liposomes have great prospects as a drug carrier.
当前脂质体载体在临床应用中的一个关键问题是包封药物的缓释特性。我们开发了由聚二乙炔（PDA）脂质和其他类型脂质组成的新型荧光pH敏感聚合脂质体。含有10,12-二十五碳二炔酸（PCDA）、1,2-二油酰基-sn-甘油-3-磷酸乙醇胺（DOPE）和N-棕榈酰高半胱氨酸（PHC）的单层脂质体被装载了氨苄青霉素。当培养基pH从7降至4时，这些脂质体迅速相互融合。对聚合脂质体进行了粒度分布表征。随着pH降低，脂质体大小从110.0±19.3nm增加到2046.7±487.4nm，增加了约20倍。二乙炔脂质的交联可防止药物泄漏，并且包封的药物可在酸性pH条件下瞬间释放。在酸性pH条件下，氨苄青霉素在4小时内从脂质体中几乎完全释放（74.4±3.9%），并通过高效液相色谱法分析氨苄青霉素的释放量。最后，通过在大肠杆菌菌苔上出现噬菌斑观察治疗效果，并从噬菌斑拍摄PDA脂质体的荧光图像以监测药物释放。结果，本研究表明这种新型pH敏感聚合脂质体作为药物载体具有广阔前景。
