Institut für Biomedizinische Technik und Informatik, Technische Universität Ilmenau, Germany.
Nanotechnology. 2020 Dec 4;31(49):495101. doi: 10.1088/1361-6528/abb0b4.
This paper elucidates the feasibility of magnetic drug targeting to the eye by using magnetic nanoparticles (MNPs) to which pharmaceutical drugs can be linked. Numerical simulations revealed that a magnetic field gradient of 20 T m seems to be promising for dragging magnetic multicore nanoparticles of about 50 nm into the eye. Thus, a targeting magnet system made of superconducting magnets with a magnetic field gradient at the eye of about 20 T m was simulated. For the proof-of-concept tissue experiments presented here the required magnetic field gradient of 20 T m was realized by a permanent magnet array. MNPs with an optimized multicore structure were selected for this application by evaluating their stability against agglomeration of MNPs with different coatings in water for injections, physiological sodium chloride solution and biological media such as artificial tear fluid. From these investigations, starch turned out to be the most promising coating material because of its stability in saline fluids due to its steric stabilization mechanism. To evaluate the passage of MNPs through the sclera and cornea of the eye tissues of domestic pigs (Sus scrofa domesticus), a three-dimensionally printed setup consisting of two chambers (reservoir and target chamber) separated by the eye tissue was developed. With the permanent magnet array emulating the magnetic field gradient of the superconducting setup, experiments on magnetically driven transport of the MNPs from the reservoir chamber into the target chamber via the tissue were performed. The resulting concentration of MNPs in the target chamber was determined by means of quantitative magnetic particle spectroscopy. It was found that none of the tested particles passed the cornea, but starch-coated particles could pass the sclera at a rate of about 5 ng mm within 24 h. These results open the door for future magnetic drug targeting to the eye.
本文通过使用可以连接药物的磁性纳米粒子 (MNPs),阐明了将药物靶向眼部的可行性。数值模拟表明,20 T m 的磁场梯度似乎有望将约 50nm 的磁性多核纳米颗粒拖入眼睛。因此,模拟了由具有约 20 T m 眼部磁场梯度的超导磁体组成的靶向磁铁系统。为了进行本文提出的组织实验验证,通过永磁体阵列实现了 20 T m 的所需磁场梯度。选择具有优化多核结构的 MNPs 用于此项应用,通过评估不同涂层的 MNPs 在注射用水、生理氯化钠溶液和人工泪液等生物介质中的团聚稳定性来实现。在此项研究中,淀粉由于其空间稳定机制而在盐溶液中稳定,因此成为最有前途的涂层材料。为了评估 MNPs 通过家猪(Sus scrofa domesticus)眼部组织的巩膜和角膜的穿透情况,开发了一个由两个腔室(储液器和靶腔室)组成的三维打印装置,该装置由眼部组织隔开。通过模拟超导装置磁场梯度的永磁体阵列,进行了通过组织将 MNPs 从储液器腔室驱动到靶腔室的磁性输送实验。通过定量磁粒子光谱法确定了靶腔室中 MNPs 的浓度。结果发现,没有任何测试的颗粒穿透了角膜,但是淀粉涂层的颗粒在 24 小时内可以以约 5ng/mm 的速率穿透巩膜。这些结果为未来将药物靶向眼部开辟了道路。
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