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.
|Number of pages||12|
|State||Published - Apr 2013|
Bibliographical noteFunding Information:
We thank the USC NanoBiophysics Core Facility. This work was supported by National Institutes of Health grants ( R01AI068978 and P01CA132681 ), a translational acceleration grant from the Joint Center for Translational Medicine , the USC Department of Radiology , the National Cancer Institute ( P30CA014089 ), and a grant from the Ming Hsieh Institute for Research on Engineering Medicine for Cancer .
- Cancer therapy
- Crosslinked multilamellar liposome
- Intracellular trafficking
- Positron emission tomography (PET)