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含有萜烯渗透促进剂的经鼻PLGA纳米颗粒：用于增强脑药物递送的膜重塑和紧密连接调节

Transnasal PLGA Nanoparticles with Terpene Permeation Enhancers: Membrane Remodeling and Tight Junction Modulation for Enhanced Brain Drug Delivery.

作者信息

Zhang Yi, Guo Zishuo, Zhang Haitong, Wei Hongmei, Wang Tieshan, Du Shouying, Li Pengyue

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

出版信息

Int J Mol Sci. 2025 Apr 18;26(8):3861. doi: 10.3390/ijms26083861.

DOI:10.3390/ijms26083861
PMID:40332504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12027855/
Abstract

Nasal nanodrug delivery has gained prominence as a non-invasive method for administering therapeutic agents to the brain. However, the limited nasal cavity volume and the low drug loading capacity of nanoparticles contribute to a reduced accumulation of the drug within the brain tissue. Therefore, the aim of the present study was to investigate the role of the drug delivery combination "transnasal route + nanoparticle drug delivery system + chemical osmosis technology" in promoting drug accumulation in the brain. We constructed an in vitro olfactory sheath cell model based on the direct nose-brain pathway and a vascular endothelial cell model based on the indirect pathway, and investigated the transport behaviors and mechanisms of Poly(lactic-co-glycolicacid)-Nanoparticles (PLGA-NPs) in combination with two terpene aroma constituents (menthol and curcumol). Menthol and curcumol significantly improved the intracellular accumulation of PLGA-NPs, which may be related to changes in the endocytosis pathway and intercellular tight junction proteins. Meanwhile, the results of laser scanning confocal microscopy and atomic force microscopy showed that menthol and curcumol disrupted different tight junction proteins of vascular endothelial cells, and the biomechanical properties (e.g., rigidity and roughness) of the olfactory sheath cells and vascular endothelial cell cytomembranes were also greatly changed. The delivery system of "transnasal route + nanoparticle drug delivery system + chemical osmosis technology" has great potential for intranasal delivery of drugs for the treatment of brain diseases.

摘要

鼻腔纳米药物递送作为一种向大脑给药的非侵入性方法已受到广泛关注。然而，鼻腔容积有限以及纳米颗粒的药物负载能力较低，导致药物在脑组织中的蓄积减少。因此，本研究的目的是探讨“经鼻途径+纳米颗粒药物递送系统+化学渗透技术”这种药物递送组合在促进药物在大脑中蓄积方面的作用。我们构建了基于直接鼻脑通路的体外嗅鞘细胞模型和基于间接通路的血管内皮细胞模型，并研究了聚乳酸-羟基乙酸共聚物纳米颗粒（PLGA-NPs）与两种萜类香气成分（薄荷醇和莪术醇）联合使用时其转运行为及机制。薄荷醇和莪术醇显著提高了PLGA-NPs在细胞内的蓄积，这可能与内吞途径和细胞间紧密连接蛋白的变化有关。同时，激光扫描共聚焦显微镜和原子力显微镜的结果表明，薄荷醇和莪术醇破坏了血管内皮细胞不同的紧密连接蛋白，嗅鞘细胞和血管内皮细胞膜的生物力学特性（如硬度和粗糙度）也发生了很大变化。“经鼻途径+纳米颗粒药物递送系统+化学渗透技术”的递送系统在经鼻递送治疗脑部疾病的药物方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/d3b06c1a1ea3/ijms-26-03861-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/0910f0e1ab8d/ijms-26-03861-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/cb98e644b60f/ijms-26-03861-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/d3b06c1a1ea3/ijms-26-03861-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/0910f0e1ab8d/ijms-26-03861-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/132930e175c6/ijms-26-03861-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/53e4c36ff5b7/ijms-26-03861-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/cb98e644b60f/ijms-26-03861-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1814/12027855/d3b06c1a1ea3/ijms-26-03861-g007.jpg

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