Ocular Biodistribution Studies Using Molecular Imaging

Abstract

Classical methodologies used in ocular pharmacokinetics studies have difficulties to obtain information about topical and intraocular distribution and clearance of drugs and formulations. This is associated with multiple factors related to ophthalmic physiology, as well as the complexity and invasiveness intrinsic to the sampling. Molecular imaging is a new diagnostic discipline for in vivo imaging, which is emerging and spreading rapidly. Recent developments in molecular imaging techniques, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), allow obtaining reliable pharmacokinetic data, which can be translated into improving the permanence of the ophthalmic drugs in its action site, leading to dosage optimisation. They can be used to study either topical or intraocular administration. With these techniques it is possible to obtain real-time visualisation, localisation, characterisation and quantification of the compounds after their administration, all in a reliable, safe and non-invasive way. None of these novel techniques presents simultaneously high sensitivity and specificity, but it is possible to study biological procedures with the information provided when the techniques are combined. With the results obtained, it is possible to assume that molecular imaging techniques are postulated as a resource with great potential for the research and development of new drugs and ophthalmic delivery systems.

Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop

“…PET/CT imaging is a relatively new imaging modality that provides a quantifiable signal on the pharmacokinetic profile of the topically administered radiopharmaceutical. In this way, it allows to obtain a signal in the eye after an eye drop instillation and its subsequent follow-up at different study times, and to be able to follow the biodistribution of the formulation in the nasolacrimal duct and nasal cavity [ 62 ].…”

“…The positron emission tomography (PET) and computed tomography (CT) procedures for conducting the radiolabeling of the formulations and the quantitative ocular permanence study were described in our previous works [ 15 , 61 , 62 ]. Briefly, PET and CT images were acquired using the Albira PET/CT Preclinical Imaging System (Bruker Biospin ® ; Woodbridge, Connecticut, USA).…”

Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations

“…The factors that affect the drug distribution in the vitreous humor are predominantly its diffusion through the vitreous, the effect of the convective flow and the possible drug interactions with the vitreous humor elements. Moreover, other ocular barriers may limit the drug passage depending on the target site within the vitreous cavity [24].…”

Biopharmaceutical Assessment of Dexamethasone Acetate-Based Hydrogels Combining Hydroxypropyl Cyclodextrins and Polysaccharides for Ocular Delivery

“…The biopermanence of Gels A and B, DXMa (10 mg/mL)/HPβCD (600 mg/mL), DXMa (30 mg/mL)/HPγCD (600 mg/mL), VISMED ® , and CELLUVISC ® was characterized on the ocular surface of rats by 18 F-FDG radiolabeling followed by radioactivity in PET over 5 h (300 min) ( Figure 7 ). It is a non-invasive tool for pharmacokinetic studies of clearance of topical ocular drug delivery systems [ 22 , 38 ]. In the present study, all the formulations tested presented a higher residence than the control solution of Balanced Salt Solution (BSS), whose composition is close to tears.…”