Lactoferrin-decorated vs PEGylated zein nanospheres for combined aromatase inhibitor and herbal therapy of breast cancer.

Autor:	El-Lakany SA; a Department of Industrial Pharmacy, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt., Elgindy NA; a Department of Industrial Pharmacy, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt., Helmy MW; b Department of Pharmacology and Toxicology, Faculty of Pharmacy , Damanhur University , El-Behira , Egypt.; c Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy , Alexandria University , Alexandria , Egypt., Abu-Serie MM; d Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications , Alexandria , Egypt., Elzoghby AO; a Department of Industrial Pharmacy, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt.; c Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy , Alexandria University , Alexandria , Egypt.; e Division of Engineering in Medicine, Department of Medicine , Brigham and Women's Hospital, Harvard Medical School , Boston , MA , USA.; f Harvard-MIT Division of Health Sciences and Technologies , Cambridge , MA , USA.
Jazyk:	angličtina
Zdroj:	Expert opinion on drug delivery [Expert Opin Drug Deliv] 2018 Sep; Vol. 15 (9), pp. 835-850. Date of Electronic Publication: 2018 Aug 10.
DOI:	10.1080/17425247.2018.1505858
Abstrakt:	Objectives: Herein, we propose combined aromatase inhibitor and herbal therapy of breast cancer as a synergistic therapeutic modality. Methods: Zein nanospheres were prepared by phase separation for co-delivery of exemestane and luteolin. To enhance their tumor-targeting capability, the nanospheres were coated with PEGylated phospholipids and lactoferrin for passive and active targeting, respectively. Results: The developed nanospheres demonstrated a small particle size and controlled drug release. In addition, the nanospheres revealed high serum stability, acceptable hemocompatibility, and good physical stability. Moreover, a 5-fold scale-up of zein nanospheres could be enabled followed by spray-drying using 2.5% mannitol as a drying adjuvant. PEGylated and lactoferrin-targeted nanospheres showed enhanced cytotoxicity against MCF-7 and 4T1 breast cancer cells with higher selectivity to cancer cells rather than normal fibroblasts. The in-vivo pharmacokinetics and anti-tumor efficacy confirmed the superiority of zein nanospheres particularly after PEGylation compared to free drug(s). The enhanced anti-cancer activity of nanocarriers was revealed as prolonged circulation half-life, lower % change in tumor volume, reduced expression of aromatase, Cyclin D1 and VEGF markers as well as amplified apoptosis and necrosis. Conclusion: Overall, combined delivery of aromatase inhibitors and herbal drugs via tumor-targeted zein nanospheres could serve as a promising strategy for breast cancer therapy.
Databáze:	MEDLINE
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