“He that is strucken blind cannot forget the precious treasure of his eyesight lost,” Shakespeare observes. The treatment of eye diseases is essential to enhance the quality of life at all stages. The delivery of drugs into the human eye is not easy due to the unique anatomy and physiology of this sense organ. Long-term drug administration is often required, stretching across months and even years.
Intravitreal delivery, developed in 1911 by Ohm, is now one of the most commonly used methods to deliver drugs into the eye. It involves injecting the drug into a gel-like substance called vitreous humour that fills the eye cavity between the lens and the retina.
In patients who have undergone retinal surgery, the gel-like vitreous humour is removed and replaced by artificial liquids that are less viscous than the natural gel. When a drug is administered to such vitreous humour substitutes, it must move through the liquid and reach the target spot (usually the retina) for the medicine to take effect. Natural diffusion is a slow process, and the drug may take several hours to days to reach effective levels at the target location.
Prof. Arunn Narasimhan and Mr Shrinivas Vibhute from the Heat Transfer and Thermal Power Laboratory, Dept of Mechanical Engineering, IIT Madras, are studying methods to enhance the delivery of intravitreally administered drugs to the target spot. For this, they consider convection-assisted diffusion, rather than natural diffusion alone.
In prior studies, Prof. Narasimhan and his students performed simulation studies to show that applying heat to the vitreous humour mimics through laser irradiation can help circulate the injected drug, thereby allowing better and faster delivery at the target location. Mr. Vibhute designed an experimental setup to prove this.
The setup consisted of a glass eye in realistic dimensions. Water and silicone oil represented the vitreous humour substitutes used in real life. A heater was used to mimic laser heating, and a dye was used as a proxy for the administered drug.
In a series of experiments, the dye was injected at two specific locations: near the lens and at the bottom of the eye cavity. Concentration measurements were taken at two points on the retinal surface—the top portion and the central retinal pigmented epithelium (RPE) area, without heating and after the application of heat.
The results showed that on applying heat, the heat-induced movement of the liquid – convection – resulted in faster dye distribution. While it took 12 hours for the drug to reach a certain concentration at the retina under pure diffusion, it took a mere 12 minutes with the application of heat. The drug concentration at the target retinal region was also 56.25 times greater with convection-assisted delivery compared to pure diffusion.
These findings show that by applying mild heat to the retinal surface through laser irradiation, convection-assisted diffusion can be initiated, which facilitates accelerated drug transport from the injection site to the targeted spot on the retina. The heat needed to enhance drug distribution is mild enough to not cause any damage to the eye.
This innovative approach holds the potential to enhance treatment effectiveness and thereby reduce the need for multiple and frequent injections as is currently needed.
Article by Akshay Anantharaman
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