ArticlePharmaceutical research2025
Effect of Molecular Size on Ocular Drug Distribution After Intravitreal Injection Using Computed Tomography and Mathematical Spatial Modeling.
Article in Pharmaceutical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
purposeIntravitreal injection is an administration route for ocular therapeutics of different molecular sizes, including antibodies, antisense oligonucleotides, and adeno-associated viruses. The purpose of this study was to identify the effect of molecular size on ocular drug distribution after intravitreal injection by computed tomography (CT) and to construct a mathematical model for clinical dosage and regimen optimization.
methodsContrast agents of different molecular sizes (ca. 1-110 nm) were intravitreally injected into rabbits and their distributions were visualized using CT. Subsequently, a computational spatial model of the rabbit eyeball with an intravitreal diffusion coefficient was constructed from CT images using the finite element method. The model was then extended to the human eyeball.
resultsCT images indicated that: 1) all contrast agents moved in the direction of gravity according to body position, and 2) intravitreal diffusivity decreased with increasing molecular size. The computational rabbit eyeball model successfully reproduced the CT images, and the intravitreal diffusion coefficient of each contrast agent was determined. Furthermore, simulation results with the human eyeball model suggested that maintaining the supine position after intravitreal injection provides better exposure at the macula, particularly for therapeutics with larger molecular size.
conclusionsUsing computational spatial modeling based on CT images, we identified the effect of molecular size on ocular drug distribution after intravitreal injection in humans. These findings are expected to aid the establishment of appropriate times to maintain the supine position to ensure targeted exposure in accordance with modality size, as well as the estimation of optimal clinical doses.
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