The vast majority of chemotherapy is lipid-soluble, administered intravenously. The availability of effective and selective oral delivery system would significantly contribute to patients’ quality of life. Bovine β-casein (β-CN) is an abundant milk protein that has a pronounced amphiphilic structure1, promoting it's self-assembly to stable micelles in aqueous solutions. β-CN contains 17% proline residues, leading to an open tertiary structure1 which is easily accessible to gastric proteases. In previous studies we showed the potential of β-CN micelles as oral delivery vehicles for the target-activated release of hydrophobic bio-actives cargo, as chemotherapeutic agents2, in the stomach3. In the current research we explore the possibility to use different combinations of encapsulated hydrophobic anticancer drugs (e.g. Paclitaxel, Mitoxantrone) along with their corresponding encapsulated hydrophobic chemosensitizers (e.g. Tariquidar, Ko143 respectively), which counteract multidrug resistance (MDR) mechanisms, that expel a spectrum of anticancer drugs from cancer cells, based on ATP-driven MDR efflux pumps (e.g. P-glycoprotein/ABCB1, breast cancer resistance protein/ABCG2). Hence, the rationally designed encapsulated pair is expected to display enhanced efficacy and synergy in the overcoming of MDR phenomena in gastric cancer. This novel treatment strategy will significantly promote patient compliance as it would not require medical assistance or equipment, thereby avoiding the need for multiple hospitalizations and enable treatment at the comfort of the patient's home.
1. Y. D. Livney, A. L. Schwan, D. G. Dalgleish, Journal of Dairy Science 2004, 87, 3638-3647.
2. A. Shapira, Y. G. Assaraf, Y. D. Livney, Nanomedicine: Nanotechnology, Biology and Medicine 2010, 6, 119-126.
3. A. Shapira, I. Davidson, N. Avni, Y. G. Assaraf, Y. D. Livney, European Journal of Pharmaceutics and Biopharmaceutics 2012, 80, 298-305.
mayawe@technion.ac.il
Corresponding authors: livney@technion.ac.il; assaraf@technion.ac.il
