Abstract
Purpose :
Various ocular barriers, low availability of systemic administration, and a lack of specificity, have made delivering drugs to the retina challenging. Currently, intravitreal injection is the common mode of delivery, but it is accompanied with several side effects, and is not localized to diseased areas. CD44, a cell surface adhesion receptor, is expressed in RPE, retina, Muller cells, and ganglion cells in their normal state, and overexpressed in their disease state. CD44 is known to have an affinity for the anionic polysaccharide, hyaluronic acid (HA), which enables cells to bind to and internalize HA. This study tested the hypothesis that hyaluronic acid-coated gold nanoparticles (HA-S-AuNPs) could traverse the blood-aqueous barrier (BAB) and reach the retina layers via CD44 mediated endocytosis.
Methods :
Gold nanoparticles (AuNPs) were synthesized then conjugated with end-thiolated hyaluronic acid, to yield hyaluronic acid-conjugated gold nanoparticles (HA-S-AuNPs). To explore their in vivo distribution in the posterior segment of the eye, 3 µl of HA-S-AuNPs at a concentration of 0.05 mg/ml were topically applied on mice eyes (n=3) while AuNPs were used as a control. At different times, the eyes were harvested to prepare retina sections, and the sections were imaged using confocal microscopy analysis. The detection of gold nanoparticles in the retina was also carried out quantitatively using inductively-coupled plasma mass spectrometry (ICP-MS). t test is used for data anlysis.
Results :
Confocal imaging shows that within 5 minutes of their instillation, 80 % more HA-S-AuNPs were detected in the retina compared to AuNPs. Kinetics studies of cumulative amount of gold nanoparticles showed that nanoparticles accumulation peaks at around 30 minutes in the retina. Using ICP-MS quantitative analysis, a concentration of 0.089 µg/l ± 0.031 of HA-S-AuNPs was detected in the retina (P<0.05).
Conclusions :
Our findings are consistent with the hypothesis that gold nanoparticles can overcome the physiological barriers of the eye and cross the BAB and the retina when coated with hyaluronic acid. Further investigations of nanoparticle size and hyaluronic acid molecular weight are needed to optimize the formula of HA-S-AuNPs. This approach would potentially offer a novel alternative way to provide an optimum treatment strategy while reducing treatment costs and increasing patient compliance.
This is a 2020 ARVO Annual Meeting abstract.