Seyedeh Hoda Alavizadeh
Nanotechnology Research Center, School of Pharmacy, Iran
Title: Improving liposomal cisplatin formulation: What we have learned after 4 year studies
Biography
Biography: Seyedeh Hoda Alavizadeh
Abstract
Statement of the Problem: Cisplatin is a widely used drug in cancer chemotherapy which is associated with dose-limiting side effects. Liposomes, the well-known lipid-based nanoparticles, were extensively explored to improve drug activity and reduce normal tissue toxicities of chemotherapeutics. So far, there are three cisplatin liposomes (CL) in clinical trials. Despite reducing side effects, most formulations show poor anti-tumor activity due to insufficient drug bioavailability at the tumor site. During our research project aimed at improving CL, a number of liposomes were prepared to enhance either cisplatin release or liposome uptake by the tumor cells. Methodology & Theoretical Orientation: Liposomes with lipids of different melting points and fusogenic properties were prepared by lipid film method to optimize the release of drug in vitro and in vivo in C26 mice model. The Anti-HER-2 affibody targeted liposomes were also compared with non-targeted liposomes to assess the efficacy of active targeting in murine breast tumor model. Further, in a murine model of C26, the therapeutic efficacy of thermos-sensitive liposomes with different HSPC/DPPC lipid ratios were evaluated upon various heating protocols. Findings: Results indicated that lipid components greatly affect release pattern of drug from liposomes; the fluid bilayers increased drug release but showed instability in vivo. Active targeting by HER2-affibody liposomes significantly increased cell uptake of liposomes. Also, external heat trigger prolonged the survival of animals by enhancing drug release. Conclusion & Significance: Using targeting ligand on the surface of liposome and optimizing lipid components, are valuable approaches resulting in a significant uptake and release of drug from liposome. However, the issue of optimum drug loading still remain. So, this results encourage us to initiate a new project to achieve the desired intra-liposomal drug concentration with the use of new loading method which would be highly desirable for the future development of promising CL formulation.