期刊
BIOMEDICINES
卷 10, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines10020493
关键词
intranasal; chitosan grafted micelles; blood-brain barrier; transfection; polymer; synthesis; targeted gene delivery; polyplex
资金
- National Institutes of Health (NIH) [RO1 AG051574, RF1 AG068034]
Multifunctional fatty acid grafted polymeric micelles have shown promise as an effective method for drug and gene delivery to the brain. Intranasal administration has been identified as an alternative approach to bypass the blood-brain barrier. In this research, polymeric micelles were prepared and characterized for the delivery of pVGF to the brain. The results showed that the modified chitosan polymer with mannose, Tat peptide, and oleic acid led to significantly higher expression of pVGF in primary astrocytes and neurons compared to intravenous administration. Intranasal administration also resulted in significantly higher pVGF expression compared to intravenous administration. These findings suggest that multifunctional polymeric micelles, especially those tagged with mannose and Tat ligands, are effective platforms for delivering pVGF to the brain.
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 < 0.05) higher VGF expression was observed in primary astrocytes and neurons using the mannose, Tat peptide, and oleic acid grafted chitosan polymer. Compared to intravenous administration, intranasal administration of pVGF in polyplex formulation led to significantly (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.
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