Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymeric Micelles for Improved Gene Delivery of VGF to the Brain through Intranasal Route

Abstract

Multifunctional fatty acid grafted polymeric micelles are an effective and promising approach for drug and gene delivery to the brain. An alternative approach to bypass the blood–brain barrier is administration through intranasal route. Multifunctional fatty acid grafted polymeric micelles were prepared and characterized for pVGF delivery to the brain. In vitro pVGF expression was analyzed in bEnd.3 cells, primary astrocytes, and neurons. Comparative in-vivo pVGF expression was analyzed to evaluate the effective route of administration between intranasal and intravenous. Biocompatible, multifunctional polymeric micelles were prepared, having an average size of 200 nm, and cationic zeta potential. Modified polymers were found to be hemo- and cyto-compatible. When transfected with the different modified chitosan formulations, significantly (p p < 0.05) higher pVGF expression. Developed multifunctional polymeric micelles were an effective pVGF delivery platform to the brain. Mannose and Tat ligand tagging improved the pVGF delivery to the brain.

Keywords

• intranasal
• chitosan grafted micelles
• blood–brain barrier
• transfection
• polymer
• synthesis