Main author: Manisha Prajapati
Institution or Company: University of Iceland
Co-Authors, Institution or Company:
François Paquet-Durand, Institute for Ophthalmic Research, University of Tübingen. Gustav Christensen2, Institute for Ophthalmic Research, University of Tübingen. Thorsteinn Loftsson, University of Iceland.
Introduction: Cyclodextrins (CDs) are widely used as pharmaceutical excipients for formulation purposes. In recent times, studies have shown that CDs can form complexes with cholesterol. This has paved the way for using CDs as drugs in retinal diseases like Stargardt disease and retinal artery occlusion, where CDs could absorb cholesterol lumps. But, studies on the retinal toxicity of CDs are limited. The purpose of this study was to examine the retinal toxicity of different βCD derivatives and their localization within the retinal tissues.
Methods: We performed cytotoxicity studies with HPβCD and RMβCD, using wild-type mouse retinal explants, the TUNEL assay, and confocal microscopy.
Results: RMβCD was found to be more toxic to retinal explants compared to HPβCD. Studies done with fluorescent forms of the same CDs showed that both CDs can penetrate deep into the inner nuclear layer of the retina, with some uptake by Müller cells.
Conclusions: The retina could safely tolerate as high as 10mM HPβCD. The results suggest that HPβCD is a safer option than RMβCD for retinal drug delivery and may advance the use of CDs in development of drugs designed for intravitreal administration.
