Cong Huijing, Hu Jing, Wang Jing, Chang Baiyu, Li Rongtao, Cui Xinran, Zhang Chenghao, Ji Hongyu, Lin Congcong, Tang Jingling, Liu Jiaxin
Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150086, China.
Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150086, China.
Int J Pharm. 2025 Jan 25;669:125054. doi: 10.1016/j.ijpharm.2024.125054. Epub 2024 Dec 10.
Parkinson's disease confronts challenges in drug delivery due to the blood-brain barrier. Intranasal delivery bypasses the blood-brain barrier for improved drug bioavailability, yet narrow nasal space and brief retention time hinder clinical applicability. We conducted a Bromocriptine Mesylate-loaded PLGA nanoparticles co-modified with low molecular weight protamine (LMWP) and lactoferrin (Lf) (LMWP/Lf-BCM-NPs) for nose-to-brain delivery. The resulting LMWP/Lf-BCM-NPs were uniform spheres with an average size of 248.53 ± 16.25 nm and zeta potential of -2.63 ± 0.74 mV. Fourier transform infrared spectroscopy confirmed LMWP and Lf attachment. The co-modified nanoparticles showed improving cellular transport and good viability. The LMWP/Lf-BCM-NPs showed increased brain targeting efficiency in mice. In haloperidol-induced Parkinson mouse models, the LMWP/Lf-BCM-NPs showed increased brain targeting efficiency, enhanced behavioral regulatory effects, enhanced antioxidant effects and neuroprotection effects. This study paves the way for a novel, non-invasive brain-targeted therapy, offering a promising avenue for Parkinson's disease clinical treatment.
由于血脑屏障的存在，帕金森病在药物递送方面面临挑战。鼻内给药绕过血脑屏障以提高药物生物利用度，但鼻腔空间狭窄和滞留时间短暂阻碍了其临床应用。我们制备了负载甲磺酸溴隐亭的聚乳酸-羟基乙酸共聚物纳米粒（PLGA NPs），该纳米粒用低分子量鱼精蛋白（LMWP）和乳铁蛋白（Lf）进行了共修饰（LMWP/Lf-BCM-NPs），用于鼻脑递送。所得的LMWP/Lf-BCM-NPs为均匀的球体，平均粒径为248.53±16.25 nm，zeta电位为-2.63±0.74 mV。傅里叶变换红外光谱证实了LMWP和Lf的附着。共修饰的纳米粒显示出改善的细胞转运和良好的活力。LMWP/Lf-BCM-NPs在小鼠中显示出提高的脑靶向效率。在氟哌啶醇诱导的帕金森病小鼠模型中，LMWP/Lf-BCM-NPs显示出提高的脑靶向效率、增强的行为调节作用、增强的抗氧化作用和神经保护作用。本研究为一种新型的非侵入性脑靶向治疗铺平了道路，为帕金森病的临床治疗提供了一条有前景的途径。
