Lima Alexandre Ferreira, Amado Isabel R, Pires Liliana R
INL-International Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal.
Polymers (Basel). 2020 Dec 21;12(12):3063. doi: 10.3390/polym12123063.
The administration of specific antigens is being explored as a mean to re-establish immunological tolerance, namely in the context of multiple sclerosis (MS). PLP139-151 is a peptide of the myelin's most abundant protein, proteolipid protein (PLP), which has been identified as a potent tolerogenic molecule in MS. This work explored the encapsulation of the peptide into poly(lactide--glycolide) nanoparticles and its subsequent incorporation into polymeric microneedle patches to achieve efficient delivery of the nanoparticles and the peptide into the skin, a highly immune-active organ. Different poly(d,l-lactide--glycolide) (PLGA) formulations were tested and found to be stable and to sustain a freeze-drying process. The presence of trehalose in the nanoparticle suspension limited the increase in nanoparticle size after freeze-drying. It was shown that rhodamine can be loaded in PLGA nanoparticles and these into poly(vinyl alcohol)-poly(vinyl pyrrolidone) microneedles, yielding fluorescently labelled structures. The incorporation of PLP into the PLGA nanoparticles resulted in nanoparticles in a size range of 200 µm and an encapsulation efficiency above 20%. The release of PLP from the nanoparticles occurred in the first hours after incubation in physiological media. When loading the nanoparticles into microneedle patches, structures were obtained with 550 µm height and 180 µm diameter. The release of PLP was detected in PLP-PLGA.H20 nanoparticles when in physiological media. Overall, the results show that this strategy can be explored to integrate a new antigen-specific therapy in the context of multiple sclerosis, providing minimally invasive administration of PLP-loaded nanoparticles into the skin.
目前正在探索给予特定抗原来重新建立免疫耐受，即在多发性硬化症（MS）的背景下。PLP139 - 151是髓鞘中最丰富的蛋白质——蛋白脂蛋白（PLP）的一种肽段，它已被确定为MS中一种有效的致耐受性分子。这项工作探索了将该肽段封装到聚（丙交酯 - 乙交酯）纳米颗粒中，并随后将其掺入聚合物微针贴片中，以实现纳米颗粒和肽段向皮肤（一个高度免疫活性器官）的有效递送。测试了不同的聚（d，l - 丙交酯 - 乙交酯）（PLGA）配方，发现它们是稳定的并且能够承受冷冻干燥过程。纳米颗粒悬浮液中存在海藻糖限制了冷冻干燥后纳米颗粒尺寸的增加。结果表明，罗丹明可以负载在PLGA纳米颗粒中，并且这些纳米颗粒可以掺入聚（乙烯醇） - 聚（乙烯基吡咯烷酮）微针中，产生荧光标记结构。将PLP掺入PLGA纳米颗粒中导致纳米颗粒尺寸范围在200 µm，包封效率高于20％。在生理介质中孵育后的最初几个小时内，PLP从纳米颗粒中释放出来。当将纳米颗粒加载到微针贴片中时，获得了高度为550 µm，直径为180 µm的结构。在生理介质中时，在PLP - PLGA.H20纳米颗粒中检测到了PLP的释放。总体而言，结果表明可以探索这种策略，以便在多发性硬化症的背景下整合一种新的抗原特异性疗法，将负载PLP的纳米颗粒以微创方式给药到皮肤中。
