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基于聚合物的姜黄素纳米粒子的设计与开发用于药物输送增强及潜在整合入神经导管

Design and Development of a Polymeric-Based Curcumin Nanoparticle for Drug Delivery Enhancement and Potential Incorporation into Nerve Conduits.

机构信息

NanoScience Technology Center, University of Central Florida, Orlando, FL 32826, USA.

Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32826, USA.

出版信息

Molecules. 2024 May 12;29(10):2281. doi: 10.3390/molecules29102281.

DOI:10.3390/molecules29102281
PMID:38792144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11124517/
Abstract

Peripheral nerve injuries (PNI) impact millions of individuals in the United States, prompting thousands of nerve repair procedures annually. Nerve conduits (NC) are commonly utilized to treat nerve injuries under 3 cm but larger gaps still pose a challenge for successful peripheral nerve regeneration (PNR) and functional recovery. This is partly attributed to the absence of bioactive agents such as stem cells or growth factors in FDA-approved conduits due to safety, harvesting, and reproducibility concerns. Therefore, curcumin, a bioactive phytochemical, has emerged as a promising alternative bioactive agent due to its ability to enhance PNR and overcome said challenges. However, its hydrophobicity and rapid degradation in aqueous solutions are considerable limitations. In this work, a nanoscale delivery platform with tannic acid (TA) and polyvinylpyrrolidone (PVP) was developed to encapsulate curcumin for increased colloidal and chemical stability. The curcumin nanoparticles (CurNPs) demonstrate significantly improved stability in water, reduced degradation rates, and controlled release kinetics when compared to free curcumin. Further, cell studies show that the CurNP is biocompatible when introduced to neuronal cells (SH-SY5Y), rat Schwann cells (RSC-S16), and murine macrophages (J774 A.1) at 5 μM, 5 μM, and 10 μM of curcumin, respectively. As a result of these improved physicochemical properties, confocal fluorescence microscopy revealed superior delivery of curcumin into these cells when in the form of CurNPs compared to its free form. A hydrogen peroxide-based oxidative stress study also demonstrated the CurNP's potential to protect J774 A.1 cells against excessive oxidative stress. Overall, this study provides evidence for the suitability of CurNPs to be used as a bioactive agent in NC applications.

摘要

周围神经损伤(PNI)影响了美国数以百万计的个体,促使每年进行数千次神经修复手术。神经导管(NC)通常用于治疗 3 厘米以下的神经损伤,但较大的间隙仍然对成功的周围神经再生(PNR)和功能恢复构成挑战。这在一定程度上是由于 FDA 批准的导管中缺乏生物活性物质,如干细胞或生长因子,这是出于安全性、收获和重现性的考虑。因此,姜黄素作为一种有前途的生物活性替代物,已成为研究热点,因为它能够增强 PNR 并克服上述挑战。然而,其疏水性和在水溶液中的快速降解是相当大的限制。在这项工作中,开发了一种带有单宁酸(TA)和聚乙烯吡咯烷酮(PVP)的纳米级递送平台,以包封姜黄素,从而提高胶体和化学稳定性。与游离姜黄素相比,姜黄素纳米颗粒(CurNPs)在水中表现出显著提高的稳定性、降低的降解速率和受控的释放动力学。此外,细胞研究表明,当以 5 μM、5 μM 和 10 μM 的游离姜黄素浓度将 CurNP 引入神经元细胞(SH-SY5Y)、大鼠雪旺细胞(RSC-S16)和小鼠巨噬细胞(J774 A.1)时,CurNP 是生物相容的。由于这些改进的物理化学性质,共聚焦荧光显微镜显示,与游离形式相比,CurNP 以更优的方式将姜黄素递送到这些细胞中。基于过氧化氢的氧化应激研究也表明,CurNP 有潜力保护 J774 A.1 细胞免受过度氧化应激。总的来说,这项研究为 CurNP 作为 NC 应用中的生物活性物质的适用性提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a6/11124517/f4198991638d/molecules-29-02281-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a6/11124517/f4198991638d/molecules-29-02281-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a6/11124517/352095b00665/molecules-29-02281-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a6/11124517/649b3a06f1cb/molecules-29-02281-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a6/11124517/33d389e4fb75/molecules-29-02281-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a6/11124517/c53f2ca0d522/molecules-29-02281-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06a6/11124517/f4198991638d/molecules-29-02281-g005.jpg

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