الفهرس 
Analysis of varianceOnly 14 pages are availabe for public view
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Abstract
Fisetin is a potent phytochemical suffering from poor physicochemical properties. The current work is elaborated to develop novel bio-inspired lipid nanoparticles that are partially mimicking lipoproteins in their lipid composition in attempt to improve Fisetin delivery into breast cancer. The developed lipoproteins inspired nanoparticles (ULP) were then decorated with specific CD-44 targeting biopolymers. Both uncoated and biopolymer coated nanosystems were appraised for their pharmaceutical and therapeutic performance. All nanoformulations showed excellent fisetin encapsulation efficiency with sustained drug release over 24 h. In-vitro cell line studies against MDA-MB-231 revealed an average of 4-fold increase in all nanoformulations cytotoxicity compared with free drug. Preclinical studies in Ehrlich ascites tumor bearing mice revealed that intravenous administration of optimized fisetin-loaded nanoformulations (10 mg/kg) could significantly reduce tumor growth compared with free drug without any systemic toxicity on major organs. Furthermore, results of immunohistochemical assay proved the potential of unmodified lipoprotein inspired nanosystem (ULP) to reduce breast cancer growth in a comparable efficacy to the CD44-targeting nanosystems. To conclude, lipoproteins-partially mimicking nanoparticles either solely or coupled with active targeting ligands can be utilized as
biocompatible, tumor-targeting nanomedicines for controlled delivery of fisetin to breast cancer.