Modeling of Anticancer Drug Delivery By Temperature-Sensitive Liposomes

Abstract

Cytotoxic anticancer drugs are used to treat cancer, particularly tumors. These drugs themselves do not distinguish between healthy and tumor cells and attack all of them. Consequently physicians and chemists investigate safer ways of delivery that minimize damage to healthy cells. One of these ways are liposomal formulations of the anticancer drugs. Liposomes are vesicles that encapsulate the drug to shield the healthy parts of the body from the toxicity of the drugs. Due to the abnormal structure of tumors, especially their leaky vasculature, these macromolecules are able to diffuse into the tumor tissue whereas the normal vasculature prevents them to move into the tissue. After reaching the diseased tissue, the liposomes release their cargo triggered by a physical or chemical process. In this thesis, we will investigate those liposomes that are activated upon entering regions of increased tissue temperature. Developing temperature-sensitive liposomes for targeted anticancer drug delivery is difficult to realize. The liposomes must be able to move far into the tumor against the interstitial pressure. The release of the drug must be triggered precisely in the tumor. We will show that the drug can move further into the tissue by diffusion. The aim of the mathematical modeling is to improve our understanding of the release and transport processes involved and (in the future) to optimize the scheduling between tissue heating and the liposome administration.