Tomas Etrych
Institute of Macromolecular Chemistry AS CR, Czech Republic
Title: Polymer based delivery systems for efficient tumor therapy
Biography
Biography: Tomas Etrych
Abstract
Beside the development of novel low-molecular-weight anti-cancer agents, new formulations of “classic” cytostatic drugs, so called drug delivery systems (DDS), including their encapsulation into liposomes and nanoparticles or covalent binding to water-soluble polymers and micelles, appear to be a very promising strategy.Described micellar and star polymer-drug conjugates are high-molecular-weight (HMW) drug conjugates designed for enhanced passive tumor accumulation and release of drug in the acidic milieu of a tumor. Th e therapeutic effi cacy of the conjugates is based on two mechanisms of selectivity toward solid tumors: I) drug accumulation in tumors driven by enhanced permeability and retention (EPR) eff ect, which results in almost 100 times higher concentration of drug in the solid tumor than in normal tissue, II) pH-dependent release of drug from polymer-drug conjugate, which releases free drug more effi ciently at a lower pH in tumors. By the in vivo noninvasive multispectral optical imaging of fl uorescently labeled copolymers we have proven that the longer circulation times of star-like copolymers in blood led to higher accumulation in tumors. Th e same phenomenon has been observed in biodistribution studies of selected drugs. Th e tumor-to-blood and tumor-to-muscle ratio for star and micellar polymerdoxorubucin conjugates increased with time, demonstrating that the conjugates passively accumulate within a tumor mass due to the EPR eff ect. Th e anti-tumor activities of linear, micellar and star copolymers containing Dox were compared using a well-defi ned model of experimental malignant tumor, mouse EL4 T cell lymphoma, inoculated in conventional mice. Th e highest effi cacy, highest percentage of LTS, was achieved during the treatment with micellar and star conjugates. Moreover, we observed that the pH-sensitive polymer-drug conjugates have the potential to induce excellent antitumor eff ect without apparent adverse eff ects.
