摘要
Cataracts are a leading cause of blindness, but the only available treatment is surgery, which may not be a viable option for many patients. Instead, pharmacological interventions that target cataractogenesis at the molecular level represent an attractive method for preventing or delaying cataract formation. Antioxidant drugs like N-(2-mercaptopropionyl)glycine may interfere with oxidative processes that lead to age-related nuclear cataracts. Nevertheless, achieving therapeutic concentrations in the lens has proven challenging. Novel delivery strategies such as functionalized nanodiamonds offer several advantages over conventional platforms in terms of stability and customizability. Therefore, we investigated the effects of three different types of functionalized nanodiamonds on the uptake and efficacy of a potential anticataract agent in a whole organ culture model of oxidative insult in the lens. Lenses treated with sodium selenite exhibited detrimental morphological changes and significantly deteriorated redox status. Lenses treated with the neat drug showed marked improvements. However, only hydroxylated nanodiamonds appeared to improve drug uptake, and their effects on lens glutathione and cysteine were modest. This work represents a critical step in understanding the anticataract effects of N-(2-mercaptopropionyl)glycine, and it suggests that other drug delivery strategies may be warranted to realize these effects in vivo.
Cataracts are a leading cause of blindness, but the only available treatment is surgery, which may not be a viable option for many patients. Instead, pharmacological interventions that target cataractogenesis at the molecular level represent an attractive method for preventing or delaying cataract formation. Antioxidant drugs like N-(2-mercaptopropionyl)glycine may interfere with oxidative processes that lead to age-related nuclear cataracts. Nevertheless, achieving therapeutic concentrations in the lens has proven challenging. Novel delivery strategies such as functionalized nanodiamonds offer several advantages over conventional platforms in terms of stability and customizability. Therefore, we investigated the effects of three different types of functionalized nanodiamonds on the uptake and efficacy of a potential anticataract agent in a whole organ culture model of oxidative insult in the lens. Lenses treated with sodium selenite exhibited detrimental morphological changes and significantly deteriorated redox status. Lenses treated with the neat drug showed marked improvements. However, only hydroxylated nanodiamonds appeared to improve drug uptake, and their effects on lens glutathione and cysteine were modest. This work represents a critical step in understanding the anticataract effects of N-(2-mercaptopropionyl)glycine, and it suggests that other drug delivery strategies may be warranted to realize these effects in vivo.
作者
Annalise Pfaff
Anna Chernatynskaya
Nuran Ercal
Annalise Pfaff;Anna Chernatynskaya;Nuran Ercal(Department of Chemistry, Missouri University of Science and Technology, Rolla, MO, USA;Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, MO, USA)
