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.
摘要：
多功能脂肪酸接枝聚合物胶束是将药物和基因递送到大脑的有效且有前途的方法。绕过血脑屏障的另一种方法是通过鼻内途径给药。制备了多功能脂肪酸接枝的聚合物胶束，并对其进行了表征，以将pVGF递送到大脑。在bEnd.3细胞中分析了体外pVGF表达，原代星形胶质细胞，和神经元。分析比较体内pVGF表达以评估鼻内和静脉内之间的有效施用途径。生物相容性,制备了多功能聚合物胶束，平均尺寸为200nm，和阳离子ζ电位。发现改性聚合物是血液和细胞相容的。当用不同的改性壳聚糖制剂转染时，使用甘露糖，在原代星形胶质细胞和神经元中观察到更高的VGF表达（p<0.05），Tat肽，和油酸接枝壳聚糖聚合物。与静脉给药相比，在复合物制剂中鼻内施用pVGF导致显著(p<0.05)更高的pVGF表达。开发的多功能聚合物胶束是有效的pVGF递送到大脑的平台。甘露糖和Tat配体标记改善了pVGF向大脑的递送。
