Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, ND 58105, USA.
Int J Mol Sci. 2023 Aug 21;24(16):13019. doi: 10.3390/ijms241613019.
Chitosan-based polymeric micelles are promising non-viral nanocarriers for safe and targeted gene delivery. Multi-functionalized chitosan polymeric micelles were prepared by grafting fatty acid, cell-penetrating peptide, and mannose on the chitosan backbone. The polymeric micelles were subjected to surface morphology and surface topography using scanning electron microscopy and atomic force microscopy, respectively. The hemotoxic profile of the prepared polymeric micelles was established against erythrocytes and was found to be <5% hemotoxic up to the concentration of 600 µg/mL. In vitro expression in primary astrocytes and neurons was analyzed. Multi-functionalized polymeric micelles produced greater ( < 0.05) transfection in astrocytes and neurons in comparison to mono-functionalized micelles. Intranasal administration of polymeric micelles/ polyplex led to significantly higher ( < 0.05) in vivo expression than chitosan and unfunctionalized polymeric micelles-treated mice groups. The outcomes of this study predict that the developed multi-functionalized polymeric micelles could be an effective and safe gene delivery platform to the brain through the intranasal route.
壳聚糖基聚合物胶束是一种很有前途的非病毒纳米载体，可用于安全靶向基因传递。通过在壳聚糖主链上接枝脂肪酸、细胞穿透肽和甘露糖，制备了多功能化壳聚糖聚合物胶束。分别使用扫描电子显微镜和原子力显微镜对聚合物胶束进行了表面形态和表面形貌分析。通过对红细胞进行测试，建立了所制备的聚合物胶束的血液毒性概况，发现其血液毒性 < 5%，最高浓度可达 600μg/ml。分析了原代星形胶质细胞和神经元中的体外表达。与单功能化胶束相比，多功能化聚合物胶束在星形胶质细胞和神经元中的转染效率更高（<0.05）。与壳聚糖和未功能化聚合物胶束处理的小鼠组相比，聚合物胶束/多聚物经鼻腔给药后，体内表达水平显著提高（<0.05）。本研究的结果表明，通过鼻腔给药，所开发的多功能化聚合物胶束可能成为一种有效的、安全的脑内基因传递平台。
