In Vivo Ocular Fluorophotometry: Delivery of Fluoresceinated Dextrans via Transscleral Diffusion in Rabbits

Berezovsky, Damian E.; Patel, Sarvar; McCarey, Bernard E.; Edelhauser, Henry F.

doi:10.1167/iovs.11-7207

Cited by 18 publications

(8 citation statements)

References 27 publications

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“…Ocular pharmacokinetic studies have provided useful information on the distribution of drugs in the eye and in the development of novel drug delivery methods. In addition to conventional pharmacokinetic approaches of tissue dissection, methods such as microdialysis (13), fluorophotometry (14), and magnetic resonance imaging (MRI) (15) have been used in the studies of ocular pharmacokinetics and to determine the routes of drug delivery and clearance after periocular, intrascleral, and intravitreal administration. Despite these recent efforts in studying the mechanisms and pharmacokinetics of ocular drug delivery, the distribution and clearance after ocular drug delivery are still difficult to predict (16).…”

Section: Introductionmentioning

confidence: 99%

Ocular Delivery of pRNA Nanoparticles: Distribution and Clearance After Subconjunctival Injection

Feng

Liu

et al. 2013

Pharm Res

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Purpose RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA of bacteriophage phi29 DNA packaging motor were previously found to be thermodynamically stable. As the nanoparticles could have potential in ocular drug delivery, the objectives in the present study were to investigate the distribution of pRNA nanoparticles after subconjunctival injection and examine the feasibility to deliver the nanoparticles to the cells of cornea and retina. Methods Alexa647-labeled pRNA nanoparticles (pRNA-3WJ and pRNA-X) and double-stranded RNA (dsRNA) were administered via subconjunctival injection in mice. Alexa647 dye was a control. Topical administration was performed for comparison. Ocular clearance of pRNA nanoparticles and dsRNA after the injection was assessed using whole-body fluorescence imaging of the eyes. The numbers of cells in the ocular tissues with nanoparticle cell internalization were determined in fluorescence microscopy of dissected eye tissues. Results After subconjunctival injection, pRNA nanoparticles and dsRNA were observed to distribute into the eyes and cleared through the lymph. pRNA-3WJ, pRNA-X, and dsRNA were found in the cells of the conjunctiva, cornea, and sclera, but only pRNA-X was in the cells of the retina. Topical administration was not effective in delivering the nanoparticles to the eye. Conclusions The pRNA nanoparticles were delivered to the cells in the eye via subconjunctival injection, and cell internalization was achieved in the cornea with pRNA-3WJ and pRNA-X and in the retina with pRNA-X. Only the X-shape pRNA-X could enter the retina.

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Section: Introductionmentioning

confidence: 99%

Ocular Delivery of pRNA Nanoparticles: Distribution and Clearance After Subconjunctival Injection

Feng

Liu

et al. 2013

Pharm Res

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“…Fluorescence measurements were performed with a modified Fluorotron Master FM-2 fluorophotometer (OcuMetrics, Mountain View, CA). A detailed description of the device and the measuring principle are published elsewhere 10–12. In brief, an optical illuminating path (excitation wavelength 420–490 nm) intersects with an optical pick-up path (emission wavelength 530–630 nm).…”

Section: Methodsmentioning

confidence: 99%

Fluorophotometric Determination of Riboflavin Concentrations in a Human Artificial Anterior Chamber Model

Iselin

Thiel

Bachmann

et al. 2019

Trans. Vis. Sci. Tech.

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PurposeCorneal cross-linking (CXL) requires an adequate corneal riboflavin impregnation, which is clinically assessed by verification of a riboflavin “flare” in the anterior chamber. We set out to replace this subjective assessment with an objective measurement method and evaluated fluorophotometry as an apparatus-based technique for riboflavin detection in the anterior chamber.MethodsIn an artificial anterior chamber model using human corneas and a modified Fluorotron fluorophotometer, we determined the detection limits of riboflavin concentrations across native corneas by comparison measurements of the same concentrations in glass cuvettes. Subsequently, standard CXL procedures with corneal application of riboflavin were simulated and the proportions of riboflavin entering the anterior chamber were measured fluorophotometrically.ResultsThe measurement results of the riboflavin dilution series in the artificial anterior chamber showed a very high concordance with the results obtained in a glass cuvette (Pitman test P = 0.329). In the CXL simulation, the mean riboflavin concentration measured in the anterior chamber increased within 15 minutes from 5 (±1) to 903 (±204) ng/mL and stood at 1089 (±56) ng/mL after 30 minutes.ConclusionsFluorophotometry is able to measure riboflavin in an artificial anterior chamber across human corneas over a wide range of concentrations and it reliably detects the increasing riboflavin signal in simulated CXL procedures.Translational RelevanceThe replacement of the subjective riboflavin detection by a technically straightforward, objective detection method might increase patient safety and treatment efficiency in CXL.

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“…It is possible to measure the effects of drugs and delivery systems on the blood ocular barrier by following the entrance of intravenous FITC-dextran to the eye. This method was demonstrated to be used to study transscleral drug delivery [98,99,100].…”

Section: Fluorescencementioning

confidence: 99%

Ocular Biodistribution Studies Using Molecular Imaging

et al. 2019

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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.

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In Vivo Ocular Fluorophotometry: Delivery of Fluoresceinated Dextrans via Transscleral Diffusion in Rabbits

Cited by 18 publications

References 27 publications

Ocular Delivery of pRNA Nanoparticles: Distribution and Clearance After Subconjunctival Injection

Ocular Delivery of pRNA Nanoparticles: Distribution and Clearance After Subconjunctival Injection

Fluorophotometric Determination of Riboflavin Concentrations in a Human Artificial Anterior Chamber Model

Ocular Biodistribution Studies Using Molecular Imaging

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