Pharmaceutica Analytica Acta

Polymer based delivery systems for efficient tumor therapy

5^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 16-18, 2015 Crowne Plaza, Dubai, UAE

Tomas Etrych1, Petr Chytil1, Milada Sirova2, Stefan Hoffman3, Thomas Muller3+, KarstenMader3, Blanka Rihova2, Karel Ulbrich1

Scientific Tracks Abstracts: Pharm Anal Acta

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. The therapeutic efficacy 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) effect, 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 efficiently at a lower pH in tumors. By the in vivo noninvasive multispectral optical imaging of fluorescently labeled copolymers we have proven that the longer circulation times of star-like copolymers in blood led to higher accumulation in tumors. The same phenomenon has been observed in biodistribution studies of selected drugs. The 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 effect. The anti-tumor activities of linear, micellar and star copolymers containing Dox were compared using a well-defined model of experimental malignant tumor, mouse EL4 T cell lymphoma, inoculated in conventional mice. The highest efficacy, 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 effect without apparent adverse effects.

Biography :

Tomas Etrych has completed his PhD at the age of 28 years from Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic (IMC). He is the group-leader of Department of Biomedicinal Polymers of IMC. He has published more than 75 papers in reputed international journals, which were cited more than 1800 times and is an author of 8 patents. His research focus is based on preparation of water-soluble and micellar drug delivery systems for effective treatment of cancer.