BETA-CASEIN NANOPARTICLES FOR ORAL DELIVERY OF HYDROPHOBIC COMPOUND COMBINATIONS

Maya Bar-Zeev ^1,2 Yehuda G. Assaraf ³ Yoav D. Livney ^1,2

¹Laboratory of Biopolymers and Food Nanotechnology, Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa
²Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa
³The Fred Wyszkowski Cancer Research Laboratory, Faculty of Biology, Technion - Israel Institute of Technology, Haifa

Bovine β-casein (β-CN) is an abundant milk protein that has a pronounced amphiphilic structure¹, promoting it's self-assembly to stable micellar structures in aqueous solutions². β-CN contains 17% proline residues, leading to an open tertiary structure¹ which is easily accessible to gastric proteases. In previous studies we introduced the potential of (β-CN) micelles as vehicles for oral delivery of hydrophobic bio-actives, including nutraceuticals³ and drugs⁴ . In this respect, many of the current chemotherapeutic agents are lipid-soluble. Hence, we have recently shown that β-CN nanoparticles can serve as oral delivery vehicles for the target-activated release of hydrophobic chemotherapeutic drug cargo in the stomach⁵. Here we explored the possibility to co-encapsulate mixtures of hydrophobic anticancer drugs (e.g. paclitaxel, mitoxantrone) along with hydrophobic chemosensitizers (e.g. Tariquidar, Kol143), which counteract multidrug resistance (MDR) mechanisms based on efflux pump proteins (e.g. P-glycoprotein/ABCB1), which expel a spectrum of anticancer drugs from cancer cells. Hence, the rationally designed pair of co‑encapsulated cytotoxic drug and chemosensitizer is expected to display enhanced efficacy and synergy in overcoming MDR in gastric cancer. This work highlights the possibilities of applying food proteins in more challenging delivery applications.

Principal Investigators: Prof. Yoav D. Livney livney@technion.ac.il and Prof. Yehuda G. Assaraf assaraf@technion.ac.il

References

1. Livney, Y. D.; Schwan, A. L.; Dalgleish, D. G., 2004, Journal of Dairy Science 87, (11), 3638-3647.

2. Mikheeva, L. M.; Grinberg, N. V.; Grinberg, V. Y.; Khokhlov, A. R.; de Kruif, C. G., Langmuir 19, (7), 2913-2921.2003,

3. Bargarum, J.; Danino, D.; Livney, Y. D., In IFT 2009, Anaheim, CA, USA, 2009.

4. Shapira, A.; Assaraf, Y. G.; Livney, Y. D., 2010, Nanomedicine: Nanotechnology, Biology, and Medicine 6, 119-126.

5. Shapira, A.; Davidson, I.; Avni, N.; Assaraf, Y. G.; Livney, Y. D., 2012, European Journal of Pharmaceutics and Biopharmaceutics 80, (2), 298-305.