Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
Biomaterials. 2013 Apr;34(12):3098-109. doi: 10.1016/j.biomaterials.2013.01.039. Epub 2013 Jan 30.
Liposomes constitute one of the most popular nanocarriers for the delivery of cancer therapeutics. However, since their potency is limited by incomplete drug release and inherent instability in the presence of serum components, their poor delivery occurs in certain circumstances. In this study, we address these shortcomings and demonstrate an alternative liposomal formulation, termed crosslinked multilamellar liposome (CML). With its properties of improved sustainable drug release kinetics and enhanced vesicle stability, CML can achieve controlled delivery of cancer therapeutics. CML stably encapsulated the anticancer drug doxorubicin (Dox) in the vesicle and exhibited a remarkably controlled rate of release compared to that of the unilamellar liposome (UL) with the same lipid composition or Doxil-like liposome (DLL). Our imaging study demonstrated that the CMLs were mainly internalized through a caveolin-dependent pathway and were further trafficked through the endosome-lysosome compartments. Furthermore, in vivo experiments showed that the CML-Dox formulation reduced systemic toxicity and significantly improved therapeutic activity in inhibiting tumor growth compared to that of UL-Dox or DLL-Dox. This drug packaging technology may therefore provide a new treatment option to better manage cancer and other diseases.
脂质体是用于输送癌症治疗药物的最受欢迎的纳米载体之一。然而，由于其效力受到不完全药物释放和血清成分存在时固有不稳定性的限制，因此在某些情况下，其传递效果不佳。在本研究中，我们解决了这些缺点，并展示了一种替代的脂质体制剂，称为交联多层脂质体（CML）。CML 具有改善的可持续药物释放动力学和增强的囊泡稳定性的特性，可实现癌症治疗药物的控制传递。CML 稳定地将抗癌药物阿霉素（Dox）封装在囊泡中，并表现出与具有相同脂质组成的单层脂质体（UL）或类似 Doxil 的脂质体（DLL）相比，药物释放速度得到显著控制。我们的成像研究表明，CML 主要通过网格蛋白依赖性途径内化，并通过内体 - 溶酶体隔室进一步运输。此外，体内实验表明，与 UL-Dox 或 DLL-Dox 相比，CML-Dox 制剂降低了全身毒性，并显著提高了抑制肿瘤生长的治疗活性。因此，这种药物包装技术可能为更好地治疗癌症和其他疾病提供新的治疗选择。
