Superiority of aromatase inhibitor and cyclooxygenase-2 inhibitor combined delivery: Hyaluronate-targeted versus PEGylated protamine nanocapsules for breast cancer therapy
| Autor: | Maged W. Helmy, Ahmed O. Elzoghby, Maha A. El-Demellawy, Shaimaa K. Mostafa, Salah A. Sheweita |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
medicine.drug_class
Pharmaceutical Science Breast Neoplasms 02 engineering and technology Pharmacology behavioral disciplines and activities Nanocapsules Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Breast cancer In vivo mental disorders medicine Animals Humans Protamines Aromatase Mice Inbred BALB C Aromatase inhibitor Cyclooxygenase 2 Inhibitors biology Aromatase Inhibitors Chemistry Letrozole 021001 nanoscience & nanotechnology medicine.disease Protamine Rats 030220 oncology & carcinogenesis MCF-7 Cells biology.protein Female Nanocarriers 0210 nano-technology medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 529:178-192 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2017.06.077 |
| Popis: | Despite several reports have revealed the beneficial effect of co-administration of COX-2 inhibitors with aromatase inhibitors in managing postmenopausal breast cancer; no nanocarriers for such combined delivery have been developed till now. Therefore, protamine nanocapsules (PMN-NCs) have been developed to co-deliver letrozole (LTZ) that inhibits aromatase-mediated estrogen biosynthesis and celecoxib (CXB) that synergistically inhibits aromatase expression. Inspired by the CD44-mediated tumor targeting ability of hyaluronate (HA), we developed HA-coated PMN-NCs (HA-NCs) via electrostatic layer-by-layer assembly. Moreover, multi-compartmental PEGylated phospholipid-CXB complex bilayer enveloping PMN-NCs (PEG-NCs) were designed for conferring biphasic CXB release from the phospholipid corona and oily core as well as enabling passive-targeting. The NCs demonstrated excellent stability, prolonged circulation and could be scaled up with the aid of spray-drying technology. Hemolysis, serum stability and cytotoxicity studies confirmed the superiority of combined LTZ-CXB nano-delivery. Mechanistically, the NCs especially HA-NCs and PEG-NCs demonstrated precious anti-tumor effects in vivo revealed as reduction in the tumor volume and aromatase level, increased apoptosis, as well as inhibition of VEGF, NF-κB and TNF-α augmented by histopathological and immunohistochemical studies. Overall, our approach provided for the first time a potential strategy for targeted LTZ-CXB combined therapy of hormone-dependent breast cancer via singular nanocapsule delivery system. |
| Databáze: | OpenAIRE |
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