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. 2023 Mar 4;15(3):843.
doi: 10.3390/pharmaceutics15030843.

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

Jon Ander Simón  1 , Emilia Utomo  2 , Félix Pareja  1 , María Collantes  3 , Gemma Quincoces  1 , Aarón Otero  3 , Margarita Ecay  3 , Juan Domínguez-Robles  2   4 , Eneko Larrañeta  2 , Iván Peñuelas  1   3
Affiliations

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

Jon Ander Simón et al. Pharmaceutics. .

Abstract

The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I- took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants.

Keywords: SPECT/CT; intranasal implant; molecular imaging; radioiodination; risperidone.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Solid supported 125I-radiolabelling of RISP via direct halogen electrophilic substitution.
Figure 2
Figure 2
Images showing silicone molds used to prepare intranasal implants (A,B). Microscopy image of a PLGA implant prepared using the silicone molds (C). Size comparison of microimplants (D).
Figure 3
Figure 3
Microimplant (red arrow) placed inside the modified catheter (A). Intranasal administration of the implant to the animal (B).
Figure 4
Figure 4
(A) Permanganate-stained TLC strips. RISP (R) remained at Rf = 0, while sodium iodide (I) advanced to the front (Rf = 1). The mixture of both compounds (R + I) showed that the mixture did not alter the individual results. (B) Representative radioTLC radiochromatogram of radiolabeled 125I-RISP at 72 h, before purification.
Figure 5
Figure 5
Fused MicroSPECT-CT images showing the location of the microimplant inside the nasal cavity. Hotter colours indicates higher concentration of radioactivity.
Figure 6
Figure 6
(A) Comparative release of radioactivity in vivo from 125I-implants. MicroSPECT-CT images clearly show a progressive decrease in the amount of radioactivity in the nasal cavity over time, both for 125I-RISP and [125I]INa implants. Hotter colours indicates higher concentration of radioactivity. The plot in (B) shows comparative quantitative values of radioactivity release as measured in the images on the left (mean ± SD).
Figure 7
Figure 7
Radioactivity release in vitro from 125I-implants are shown in (A), while (B) shows RISP release from implants as determined by HPLC (mean ± SD).
See this image and copyright information in PMC

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