Development and characterization of lipid nanocapsules loaded with iron oxide nanoparticles for magnetic targeting to the blood-brain barrier.

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Drug Delivery and Translational Research Pub Date : 2024-12-01 Epub Date: 2024-05-13 DOI:10.1007/s13346-024-01587-w
Juan Aparicio-Blanco, Carlotta Pucci, Daniele De Pasquale, Attilio Marino, Doriana Debellis, Gianni Ciofani
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Abstract

Brain drug delivery is severely hindered by the presence of the blood-brain barrier (BBB). Its functionality relies on the interactions of the brain endothelial cells with additional cellular constituents, including pericytes, astrocytes, neurons, or microglia. To boost brain drug delivery, nanomedicines have been designed to exploit distinct delivery strategies, including magnetically driven nanocarriers as a form of external physical targeting to the BBB. Herein, a lipid-based magnetic nanocarrier prepared by a low-energy method is first described. Magnetic nanocapsules with a hydrodynamic diameter of 256.7 ± 8.5 nm (polydispersity index: 0.089 ± 0.034) and a ξ-potential of -30.4 ± 0.3 mV were obtained. Transmission electron microscopy-energy dispersive X-ray spectroscopy analysis revealed efficient encapsulation of iron oxide nanoparticles within the oily core of the nanocapsules. Both thermogravimetric analysis and phenanthroline-based colorimetric assay showed that the iron oxide percentage in the final formulation was 12 wt.%, in agreement with vibrating sample magnetometry analysis, as the specific saturation magnetization of the magnetic nanocapsules was 12% that of the bare iron oxide nanoparticles. Magnetic nanocapsules were non-toxic in the range of 50-300 μg/mL over 72 h against both the human cerebral endothelial hCMEC/D3 and Human Brain Vascular Pericytes cell lines. Interestingly, higher uptake of magnetic nanocapsules in both cell types was evidenced in the presence of an external magnetic field than in the absence of it after 24 h. This increase in nanocapsules uptake was also evidenced in pericytes after only 3 h. Altogether, these results highlight the potential for magnetic targeting to the BBB of our formulation.

Abstract Image

用于血脑屏障磁性靶向的负载氧化铁纳米粒子的脂质纳米胶囊的开发和表征。
血脑屏障(BBB)的存在严重阻碍了脑部药物的输送。它的功能依赖于脑内皮细胞与其他细胞成分(包括周细胞、星形胶质细胞、神经元或小胶质细胞)的相互作用。为了促进脑部给药,纳米药物的设计利用了不同的给药策略,包括磁驱动纳米载体作为一种外部物理靶向BBB的形式。本文首次介绍了一种通过低能耗方法制备的脂基磁性纳米载体。磁性纳米胶囊的流体力学直径为 256.7 ± 8.5 nm(多分散指数:0.089 ± 0.034),ξ电位为 -30.4 ± 0.3 mV。透射电子显微镜-能量色散 X 射线光谱分析显示,氧化铁纳米颗粒被有效地封装在纳米胶囊的油性内核中。热重分析和菲罗啉比色法都表明,氧化铁在最终配方中的比例为 12%,这与振动样品磁强计分析结果一致,因为磁性纳米胶囊的比饱和磁化率是裸氧化铁纳米颗粒的 12%。在 50-300 μg/mL 的范围内,磁性纳米胶囊在 72 小时内对人脑内皮细胞 hCMEC/D3 和人脑血管周细胞株均无毒性。有趣的是,24 小时后,在有外部磁场的情况下,两种细胞类型对磁性纳米胶囊的吸收率均高于无磁场的情况。 仅 3 小时后,周细胞对纳米胶囊的吸收率也有所提高。
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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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