Nowdays, neurodegenerative diseases represent a great challenge from both the therapeutic and diagnostic points of view. Indeed, several physiological barriers of the body, including the blood brain barrier (BBB), nasal, dermal, and intestinal barriers, interpose between the development of new drugs and their effective administration to reach the target organ or target cells at therapeutic concentrations. Currently, the nose-to-brain delivery with nanoformulations specifically designed for intranasal administration is a strategy widely investigated with the goal to reach the brain while bypassing the BBB. To produce nanosystems suitable to study both in vitro and/or in vivo cells trafficking for potential nose-to-brain delivery route, we prepared and characterized two types of fluorescent poly(ethylene glycol)-methyl-ether-block-poly(lactide-co-glycolide) (PLGA–PEG) nanoparticles (PNPs), i.e., Rhodamine B (RhB) dye loaded- and grafted- PNPs, respectively. The latter were produced by blending into the PLGA–PEG matrix a RhB-labeled polyaspartamide/polylactide graft copolymer to ensure a stable fluorescence during the time of analysis. Photon correlation spectroscopy (PCS), UV-visible (UV-vis) spectroscopies, differential scanning calorimetry (DSC), atomic force microscopy (AFM) were used to characterize the RhB-loaded and RhB-grafted PNPs. To assess their potential use for brain targeting, cytotoxicity tests were carried out on olfactory ensheathing cells (OECs) and neuron-like differentiated PC12 cells. Both PNP types showed mean sizes suitable for nose-to-brain delivery (<200 nm, PDI < 0.3) and were not cytotoxic toward OECs in the concentration range tested, while a reduction in the viability on PC12 cells was found when higher concentrations of nanomedicines were used. Both the RhB-labelled NPs are suitable drug carrier models for exploring cellular trafficking in nose-to-brain delivery for short-time or long-term studies.

中文翻译：

---

mPEG-PLGA 纳米颗粒标记有负载或共轭罗丹明-B，用于潜在的鼻对脑传递

如今，从治疗和诊断的角度来看，神经退行性疾病都是一个巨大的挑战。事实上，身体的几种生理屏障，包括血脑屏障 (BBB)、鼻腔、皮肤和肠道屏障，介于新药的开发和有效给药以达到治疗浓度的靶器官或靶细胞之间。目前，使用专为鼻内给药设计的纳米制剂的鼻对脑递送是一种广泛研究的策略，其目标是绕过 BBB 到达大脑。为了生产适用于研究体外和/或体内细胞运输以进行潜在的鼻到脑递送途径的纳米系统，我们制备并表征了两种类型的荧光聚（乙二醇）-甲基-醚-嵌段-聚（丙交酯-合作-乙交酯）（PLGA-PEG）纳米颗粒（PNPs），即分别加载罗丹明B（RhB）染料和接枝的PNPs。后者是通过将 RhB 标记的聚天冬酰胺/聚丙交酯接枝共聚物混合到 PLGA-PEG 基质中来产生的，以确保在分析期间发出稳定的荧光。光子相关光谱 (PCS)、紫外-可见 (UV-vis) 光谱、差示扫描量热法 (DSC)、原子力显微镜 (AFM) 用于表征负载 RhB 和接枝 RhB 的 PNP。为了评估它们在大脑靶向方面的潜在用途，对嗅鞘细胞 (OEC) 和神经元样分化的 PC12 细胞进行了细胞毒性测试。两种 PNP 类型均显示出适合从鼻到脑传递的平均尺寸（<200 nm，PDI < 0.3），并且在测试的浓度范围内对 OEC 没有细胞毒性，而当使用更高浓度的纳米药物时，发现 PC12 细胞的活力降低。两种 RhB 标记的 NPs 都是合适的药物载体模型，用于探索从鼻到脑传递的细胞运输，以进行短期或长期研究。