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Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body

Silicone oil endotamponades provide a reservoir for drugs in the eye. Following vitrectomy surgery to treat retinal detachments, extensive diabetic retinopathy or endophthalmitis, they can be used as long-term lipophilic depots. This study aimed to investigate the physicochemical properties of intra...

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Autores principales: Hammer, Maximilian, Schickhardt, Sonja K., Merz, Patrick R., Khoramnia, Ramin, Scheuerle, Alexander F., Mier, Walter, Uhl, Philipp, Auffarth, Gerd U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319045/
https://www.ncbi.nlm.nih.gov/pubmed/35890260
http://dx.doi.org/10.3390/pharmaceutics14071364
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author Hammer, Maximilian
Schickhardt, Sonja K.
Merz, Patrick R.
Khoramnia, Ramin
Scheuerle, Alexander F.
Mier, Walter
Uhl, Philipp
Auffarth, Gerd U.
author_facet Hammer, Maximilian
Schickhardt, Sonja K.
Merz, Patrick R.
Khoramnia, Ramin
Scheuerle, Alexander F.
Mier, Walter
Uhl, Philipp
Auffarth, Gerd U.
author_sort Hammer, Maximilian
collection PubMed
description Silicone oil endotamponades provide a reservoir for drugs in the eye. Following vitrectomy surgery to treat retinal detachments, extensive diabetic retinopathy or endophthalmitis, they can be used as long-term lipophilic depots. This study aimed to investigate the physicochemical properties of intravitreally applied drugs of different lipophilicity, namely vancomycin, ceftazidime and voriconazole. For this purpose, an in vitro model of the silicone-oil-filled eye compared to porcine vitreous bodies (PVBs) was used. In a glass container, either light or heavy silicone oil or PVB was set into equilibrium with an aqueous fluid. Vancomycin, voriconazole and ceftazidime were added in concentrations commonly applied in clinical practice. The time course of the concentration of the drugs was determined in the hydrophilic phase for up to 24 h. With silicone oil present, the concentrations of vancomycin, voriconazole and ceftazidime were elevated in the aqueous humor when compared to the vitreous body (p < 0.001 for all drugs). With increasing lipophilicity, higher concentrations of the drug dissolved in silicone oil after 24 h (52.7%, 49.1% and 34.3% for vancomycin, ceftazidime and voriconazole, respectively). While no difference between lighter- and heavier-than-water silicone oil was apparent for vancomycin and ceftazidime (p = 0.17 and p = 0.72), voriconazole dissolved significantly better in the heavier-than-water silicone oil (p = 0.002). A higher-than-expected percentage of the glycopeptide vancomycin dissolved in the porcine vitreous body, possibly due to protein binding. In conclusion, silicone oils influence the drug concentration and distribution of intravitreally applied drugs depending on their lipophilicity. The addition of F6H8 used to create heavy silicone oils attenuates these effects for lipophilic drugs. Knowledge of the distribution of these intravitreally applied drugs is crucial to ensure the desired anti-infectious effect.
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spelling pubmed-93190452022-07-27 Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body Hammer, Maximilian Schickhardt, Sonja K. Merz, Patrick R. Khoramnia, Ramin Scheuerle, Alexander F. Mier, Walter Uhl, Philipp Auffarth, Gerd U. Pharmaceutics Article Silicone oil endotamponades provide a reservoir for drugs in the eye. Following vitrectomy surgery to treat retinal detachments, extensive diabetic retinopathy or endophthalmitis, they can be used as long-term lipophilic depots. This study aimed to investigate the physicochemical properties of intravitreally applied drugs of different lipophilicity, namely vancomycin, ceftazidime and voriconazole. For this purpose, an in vitro model of the silicone-oil-filled eye compared to porcine vitreous bodies (PVBs) was used. In a glass container, either light or heavy silicone oil or PVB was set into equilibrium with an aqueous fluid. Vancomycin, voriconazole and ceftazidime were added in concentrations commonly applied in clinical practice. The time course of the concentration of the drugs was determined in the hydrophilic phase for up to 24 h. With silicone oil present, the concentrations of vancomycin, voriconazole and ceftazidime were elevated in the aqueous humor when compared to the vitreous body (p < 0.001 for all drugs). With increasing lipophilicity, higher concentrations of the drug dissolved in silicone oil after 24 h (52.7%, 49.1% and 34.3% for vancomycin, ceftazidime and voriconazole, respectively). While no difference between lighter- and heavier-than-water silicone oil was apparent for vancomycin and ceftazidime (p = 0.17 and p = 0.72), voriconazole dissolved significantly better in the heavier-than-water silicone oil (p = 0.002). A higher-than-expected percentage of the glycopeptide vancomycin dissolved in the porcine vitreous body, possibly due to protein binding. In conclusion, silicone oils influence the drug concentration and distribution of intravitreally applied drugs depending on their lipophilicity. The addition of F6H8 used to create heavy silicone oils attenuates these effects for lipophilic drugs. Knowledge of the distribution of these intravitreally applied drugs is crucial to ensure the desired anti-infectious effect. MDPI 2022-06-28 /pmc/articles/PMC9319045/ /pubmed/35890260 http://dx.doi.org/10.3390/pharmaceutics14071364 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hammer, Maximilian
Schickhardt, Sonja K.
Merz, Patrick R.
Khoramnia, Ramin
Scheuerle, Alexander F.
Mier, Walter
Uhl, Philipp
Auffarth, Gerd U.
Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body
title Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body
title_full Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body
title_fullStr Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body
title_full_unstemmed Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body
title_short Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body
title_sort intravitreal application: physicochemical properties of drugs dissolved in silicone oils of different density in comparison to the porcine vitreous body
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319045/
https://www.ncbi.nlm.nih.gov/pubmed/35890260
http://dx.doi.org/10.3390/pharmaceutics14071364
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