Sarah A El-Lakany1, Nazik A Elgindy1, Maged W Helmy2,3, Marwa M Abu-Serie4, Ahmed O Elzoghby1,3,5,6. 1. a Department of Industrial Pharmacy, Faculty of Pharmacy , Alexandria University , Alexandria , Egypt. 2. b Department of Pharmacology and Toxicology, Faculty of Pharmacy , Damanhur University , El-Behira , Egypt. 3. c Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy , Alexandria University , Alexandria , Egypt. 4. d Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications , Alexandria , Egypt. 5. e Division of Engineering in Medicine, Department of Medicine , Brigham and Women's Hospital, Harvard Medical School , Boston , MA , USA. 6. f Harvard-MIT Division of Health Sciences and Technologies , Cambridge , MA , USA.
Abstract
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.
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.
Entities:
Keywords:
Breast cancer; PEGylated nanocarriers; exemestane; lactoferrin tumor targeting; luteolin; zein nanospheres
Authors: Sarah Mokhtar; Sherine N Khattab; Kadria A Elkhodairy; Mohamed Teleb; Adnan A Bekhit; Ahmed O Elzoghby; Marwa A Sallam Journal: Front Chem Date: 2022-03-22 Impact factor: 5.221
Authors: Sarah A El-Lakany; Ahmed I Abd-Elhamid; Elbadawy A Kamoun; Esmail M El-Fakharany; Wael M Samy; Nazik A Elgindy Journal: Int J Nanomedicine Date: 2019-10-16
Authors: Nabila A El-Sheridy; Riham M El-Moslemany; Alyaa A Ramadan; Maged W Helmy; Labiba K El-Khordagui Journal: Drug Deliv Date: 2021-12 Impact factor: 6.819