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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 < 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.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
The Oleic acid (OA)-g-CS-Man-Tat conjugates were synthesized sequentially; first, OA was conjugated on the CS backbone
[36,37] Targeting the brain with for treatment disorders is Surface modification of nanoparticles ligands of is neurological widely exploited to target a challenging through the common routes of administration. This is variety of disorders [36,37] Targeting the brain for treatment of neurological disorders is owing to the tight structural integrity of the of blood–brain barrier (BBB)’s architectural cells challenging through the common routes administration (i.v.(astrocytes, and oral) pericytes
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Safe drug and gene delivery to the brain persists as a major challenge, even in the presence of vast research in this field [1]. This is largely due to the protective effect of the blood–brain barrier (BBB) [2,3]. This restrictive property of the BBB keeps greater than 99%
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