Su Qin, Pu Ximing, Bai He, Chen Xianchun, Liao Xiaoming, Huang Zhongbing, Yin Guangfu
College of Materials Science and Engineering, Sichuan University, Chengdu 610064, China.
Curr Drug Deliv. 2018;15(4):585-593. doi: 10.2174/1567201814666170719111653.
Liposomes have been widely used in gene transfection and drug delivery systems due to their excellent biocompatibility and encapsulation ability, especially, the ability to deliver the gene/drug into the cells via the membrane fusion. Thermosensitive liposomes have been proven to be a precise and effective method for cancer treatment in many preclinical studies. But the imperfect crystalline arrangement between grains occurred, resulting in planar defects at the boundaries of membranes, compromising the stability of thermosensitive liposomes.
In the present study, we developed a facile method to improve the stability of ordinary thermosensitive liposomes by introducing organic-inorganic hybrid materials with local Si-O-Si net.
A cerasome forming lipid, N, N-Dihxadecyl-N'- [(3-triethoxysilyl) propyl] urea, was synthesized and then introduced into the thermosensitive lipids to form the composite liposomes (named as cera-liposomes). The effects of the cerasome forming lipid on the cera-liposomes characteristics, including the morphology, drug loading, Zeta potential and stability of vesicles, were investigated.
Cera-liposomes were thermosensitive, and they had a loading efficiency over 2 folds more than conventional thermosensitive liposomes. With the enhanced sustain of Si-O-Si, cera-liposomes were able to avoid collapsing and fusing during storage, and had a good resistance to nonionic surfactant. More than 80% drug was still retained after storage of 15 days at room temperature.
The cerasome forming lipid showed potential in improving the stability of thermosensitive liposomes. This novel kind of cera-liposomes could be a stable and effective drug carrier for anticancer applications.
脂质体因其优异的生物相容性和包封能力，特别是通过膜融合将基因/药物递送至细胞内的能力，已被广泛应用于基因转染和药物递送系统。在许多临床前研究中，热敏脂质体已被证明是一种精确有效的癌症治疗方法。但颗粒之间的晶体排列不完善，导致膜边界出现平面缺陷，影响了热敏脂质体的稳定性。
在本研究中，我们开发了一种简便的方法，通过引入具有局部Si-O-Si网络的有机-无机杂化材料来提高普通热敏脂质体的稳定性。
合成一种形成囊泡体的脂质N,N-二己基-N'-[(3-三乙氧基甲硅烷基)丙基]脲，然后将其引入热敏脂质中形成复合脂质体（命名为囊泡脂质体）。研究了形成囊泡体的脂质对囊泡脂质体特性的影响，包括形态、载药量、Zeta电位和囊泡稳定性。
囊泡脂质体具有热敏性，其载药效率比传统热敏脂质体高出2倍以上。随着Si-O-Si的增强，囊泡脂质体在储存过程中能够避免塌陷和融合，并且对非离子表面活性剂具有良好的耐受性。在室温下储存15天后，仍保留超过80%的药物。
形成囊泡体的脂质在提高热敏脂质体稳定性方面具有潜力。这种新型囊泡脂质体可能是一种用于抗癌应用的稳定有效的药物载体。
