Brain nanotargeted [131I] I-Rolapitant as a model for brain imaging: Intranasal formulation, radiolabelling, biodistribution, and comparative study

The goal of this study was to create a novel single-photon emission computed tomography (SPECT) probe that would enable the visualization of neurokinin-1 NK1 receptor systems in the brain for the precise diagnosis and follow-up of many brain-related disorders. Rolapitant (RT), a selective, high-affinity NK1 receptor antagonist, was successfully radiolabelled with the radioactive Iodine ¹³¹I with high radiolabelling efficiency after refining several parameters impacting the radiolabelling process’ efficiency. To improve the radiopharmaceutical’s bioavailability, and brain delivery and boost the diagnostic yield of the novel radiopharmaceutical formulation, [¹³¹I] I-Rolapitant was successfully fabricated in a spanlastic nanovesicle (SNV) formulation with a convenient hydrodynamic size, a reasonable biocompatibility profile, and feasible in vitro stability.

The selected formula was evaluated comparatively in a parallel biodistribution study in contrast to RT intravenous and intranasal solutions comparing brain targeting efficiency. The in vivo study revealed a high brain uptake (6.740 ± 0.09% ID/g) after 2 h post-administration which was 3fold greater than the brain uptake of [¹³¹I] I-Rolapitant intravenous solution. Regarding the Brain/Blood Ratio, [¹³¹I] I-Rolapitant SNV outperformed RT intravenous and intranasal solutions, with a maximum ratio of 2.03 reached 24 h after administration. These results suggest that the proposed spanlastic nanoform could be regarded as a promising drug vector for the transnasal delivery of radiopharmaceuticals to the brain.

Materials

RT was purchased from BDR Pharmaceuticals International (India). Iodine-131 was acquired from the Egyptian Atomic Energy Authority’s radioisotope production facility. Merck provided chloramine-T (CAT) and sodium metabisulfite (Darmstadt, Germany). From Fisher Chemical Scientific, chloroform 99% (CHCl₃) was acquired. Sigma Aldrich provided the Tween® 80, 20, and Span 60 (St. Louis, MO, USA). Sephadex G-25 M (50–150 μm), Sigma-Aldrich, USA.

Hend Fayez, Baher Daihom, Yasser Abd El-Aleem, I.T. Ibrahim, M.A. Motaleb, Brain nanotargeted [131I] I-Rolapitant as a model for brain imaging: Intranasal formulation, radiolabelling, biodistribution, and comparative study, Journal of Drug Delivery Science and Technology, 2023, 104705, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104705

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