Ahmed O Elzoghby1,2, Shaimaa K Mostafa3,4, Maged W Helmy3,5, Maha A ElDemellawy6, Salah A Sheweita7. 1. Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt. ahmed_elzoghby@alexu.edu.eg. 2. Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt. ahmed_elzoghby@alexu.edu.eg. 3. Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt. 4. Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Alexandria, Egypt. 5. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt. 6. Pharmaceutical and Fermentation Industries Development Center (PFIDC), City for Scientific Research and Tehcnological Aplications (SRTA-City), New Borg El Arab, Alexandria, 21934, Egypt. 7. Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, 21526, Egypt.
Abstract
PURPOSE: In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). METHODS: Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. RESULTS: Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core. Moreover, phospholipid coating provided protection for cationic PRM-NCs against interaction with RBCs and serum proteins enabling their systemic administration. Pharmacokinetic analysis demonstrated prolonged circulation and delayed clearance of both drugs after intravenous administration into rats. The superior anti-tumor efficacy of multi-reservoir NCs was manifested as powerful cytotoxicity against MCF-7 breast cancer cells and marked reduction in the mammary tumor volume in Ehrlich ascites bearing mice compared with free LTZ-CXB combination. Moreover, the NCs induced apoptotic caspase activation and marked inhibition of aromatase expression and angiogenic marker, VEGF as well as inhibition of both NFκB and TNFα. CONCLUSIONS: Multi-reservoir phospholipid shell coating PRM-NCs could serve as a promising nanocarrier for parenteral combined delivery of LTZ and CXB.
PURPOSE: In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). METHODS: Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. RESULTS: Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core. Moreover, phospholipid coating provided protection for cationic PRM-NCs against interaction with RBCs and serum proteins enabling their systemic administration. Pharmacokinetic analysis demonstrated prolonged circulation and delayed clearance of both drugs after intravenous administration into rats. The superior anti-tumor efficacy of multi-reservoir NCs was manifested as powerful cytotoxicity against MCF-7 breast cancer cells and marked reduction in the mammary tumor volume in Ehrlich ascites bearing mice compared with free LTZ-CXB combination. Moreover, the NCs induced apoptotic caspase activation and marked inhibition of aromatase expression and angiogenic marker, VEGF as well as inhibition of both NFκB and TNFα. CONCLUSIONS: Multi-reservoir phospholipid shell coating PRM-NCs could serve as a promising nanocarrier for parenteral combined delivery of LTZ and CXB.
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