Anatomy and Cell Biology Publications

Title

Self-assembled amphiphilic zein-lactoferrin micelles for tumor targeted co-delivery of rapamycin and wogonin to breast cancer

Authors

Sally A Sabra, Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario, Canada; Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria 21526, Egypt.
Ahmen O. Elzoghby, Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptFollow
Salah A. Shewita, Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria 21526, Egypt.
Medhat Haroun, Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria 21526, Egypt
Maged W. Helmy, Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
Maha A. Eldemellawy, Pharmaceutical and Fermentation Industries Development Center (PFIDC), City for Scientific Research and Technological Applications (SRTA-City), New Borg El Arab, 21934 Alexandria, Egypt.
Ying Xia, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada.
David Goodale, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
Alison L. Allan, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada; Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, The University of Western University, London, Ontario, Canada.
Sohrab Rohani, epartment of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario, CanadaFollow

Document Type

Article

Publication Date

7-2018

Journal

European Journal of Pharmaceutics and Biopharmaceutics

Volume

128

First Page

156

Last Page

169

URL with Digital Object Identifier

https://doi.org/10.1016/j.ejpb.2018.04.023

Abstract

Protein-based micelles have shown significant potential for tumor-targeted delivery of anti-cancer drugs. In this light, self-assembled nanocarriers based on GRAS (Generally recognized as safe) amphiphilic protein co-polymers were synthesized via carbodiimide coupling reaction. The new nano-platform is composed of the following key components: (i) hydrophobic zein core to encapsulate the hydrophobic drugs rapamycin (RAP) and wogonin (WOG) with high encapsulation efficiency, (ii) hydrophilic lactoferrin (Lf) corona to enhance the tumor targeting, and prolong systemic circulation of the nanocarriers, and (iii) glutaraldehyde (GLA)-crosslinking to reduce the particle size and improve micellar stability. Zein-Lf micelles showed relatively rapid release of WOG followed by slower diffusion of RAP from zein core. This sequential release may aid in efflux pump inhibition by WOG thus sensitizing tumor cells to RAP action. Interestingly, these micelles showed good hemocompatibility as well as enhanced serum stability owing to the brush-like architecture of Lf shell. Moreover, this combined nano-delivery system maximized synergistic cytotoxicity of RAP and WOG in terms of tumor inhibition in MCF-7 breast cancer cells and Ehrlich ascites tumor animal model as a result of enhanced active targeting. Collectively, GLA-crosslinked zein-Lf micelles hold great promise for combined RAP/WOG delivery to breast cancer with reduced drug dose, minimized side effects and maximized anti-tumor efficacy.

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