Changing the paradigm of retinal treatment through drug delivery
What:
Paper Presentation | Présentation d'article
When:
11:05 AM, Sunday 3 Jun 2018
(10 minutes)
Where:
How:
Authors: Varun Chaudhary, Ben Muirhead, Heather Sheardown
Author Disclosure Block: V. Chaudhary: Grant/research support; Novartis, Bayer, Allergan. Employment/honoraria/consulting fees; Novartis, Bayer. Membership on an advisory panel, standing committee or board of directors; Novartis, Bayer. B. Muirhead: None. H. Sheardown: None.
Abstract Body:
Purpose: To assess three novel drug delivery vehicles for therapeutic retinal injections.
Study Design: Basic science
Methods: Three techniques of delivering retinal therapeutic injections were assessed in vitro and in vivo. All were injectable and gelled in the eye following injection, although different gelation mechanism was used in each. A temperature responsive gel which is a liquid at room temperature, but gels in response to exposure to physiologic temperatures. These systems have been shown to degrade over a period of 9-12 weeks in vivo. Secondly, a poly(ethylene glycol) (PEG) based system has been developed which gels via a chemically mediated mechanism. In these systems, we explored tethering the drug via an enzymatically labile linker. Finally, a Vitamin E and PEG system which has a novel gelation mechanism based on exposure to aqueous solutions was also examined. All systems were designed to degrade following release of the drug payload.
Results: The thermally gelling system demonstrated a prolonged release (3 months or more) of avastin following an initial burst. Degradation times in excess of 9 months were observed with these systems. In the PEG based system a dexamethasone release system was tested using matrix metalloproteinases as a model enzyme. The presence of MMP led to release of the drug, demonstrating that it is possible to create a biochemically responsive system. Degradation of the gel was dependent on the presence of the enzyme. Thirdly, the Vitamin E and PEG combination system was found to release at a relatively constant rate for a period of at least 4 months.
Conclusions: It is believed that these systems of drug delivery treatments to the back of the eye have the potential to enhance treatment regimens, resulting in drug levels within the therapeutic range for extended time periods. Different drugs are appropriate for the different systems and the system must be tailored to ensure appropriate release kinetics.
Author Disclosure Block: V. Chaudhary: Grant/research support; Novartis, Bayer, Allergan. Employment/honoraria/consulting fees; Novartis, Bayer. Membership on an advisory panel, standing committee or board of directors; Novartis, Bayer. B. Muirhead: None. H. Sheardown: None.
Abstract Body:
Purpose: To assess three novel drug delivery vehicles for therapeutic retinal injections.
Study Design: Basic science
Methods: Three techniques of delivering retinal therapeutic injections were assessed in vitro and in vivo. All were injectable and gelled in the eye following injection, although different gelation mechanism was used in each. A temperature responsive gel which is a liquid at room temperature, but gels in response to exposure to physiologic temperatures. These systems have been shown to degrade over a period of 9-12 weeks in vivo. Secondly, a poly(ethylene glycol) (PEG) based system has been developed which gels via a chemically mediated mechanism. In these systems, we explored tethering the drug via an enzymatically labile linker. Finally, a Vitamin E and PEG system which has a novel gelation mechanism based on exposure to aqueous solutions was also examined. All systems were designed to degrade following release of the drug payload.
Results: The thermally gelling system demonstrated a prolonged release (3 months or more) of avastin following an initial burst. Degradation times in excess of 9 months were observed with these systems. In the PEG based system a dexamethasone release system was tested using matrix metalloproteinases as a model enzyme. The presence of MMP led to release of the drug, demonstrating that it is possible to create a biochemically responsive system. Degradation of the gel was dependent on the presence of the enzyme. Thirdly, the Vitamin E and PEG combination system was found to release at a relatively constant rate for a period of at least 4 months.
Conclusions: It is believed that these systems of drug delivery treatments to the back of the eye have the potential to enhance treatment regimens, resulting in drug levels within the therapeutic range for extended time periods. Different drugs are appropriate for the different systems and the system must be tailored to ensure appropriate release kinetics.
