Abstract
Purpose :
Retinal vascular diseases are the leading cause of blindness, with the most challenging aspect in their treatment being the lack of non-invasive treatment. The purpose of the present study is to investigate the therapeutic potential of a biodegradable hydrogel as a vector in delivering fenofibrate, a clinically proven oral drug, in treating retinal diseases.
Methods :
FB was packaged with PLGA, βCD, and CS - HA. The release kinetics, tissue bioavailability, and stability of each were compared and determined. FB-CS-HA hydrogel was incubated in a solution with various pH to mimic tear conditions nighttime to daytime, respectively. In vitro enzymatic degradation behavior of hydrogel was investigated at 0, 12, 24, 48, 96, 120, and 144 hours, and the bioavailability of FB was measured by HPLC-MS. The anti-inflammatory effect was examined in ARPE 19 cells exposed to LPS in either the presence or absence of FB loading hydrogel. The releasing speed and total releasing amount of FB in ARPE 19 cells were measured by flow cytometry. NF-κB activation and the levels of inflammatory factors of monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-alpha (TNFα) were measured.
Results :
FB was released at a therapeutic dose up to 144 hours in all three hydrogels with a 1% (w/v) loading dose. The degradation of hydrogel was slightly faster in an alkaline condition and is likely pH-sensitive. FB was released at a rather stable speed up to 96 hours in the hydrogel. Exposure of ARPE19 cell in the hydrogel to LPS increased the levels of MCP-1, ICAM-1, and TNFα in the absence of FB, whereas their levels decreased in the presence of FB. Exposure of ARPE19 cells to LPS in the hydrogel in the absence of FB elevated NF-κB phosphorylation and induced NF-κB nuclear translocation, both of which were inhibited in the presence of FB.
Conclusions :
Hydrogel contact lenses are a viable biodegradable and biocompatible tool in the delivery of clinically-proven drugs in the treatment of retinal diseases.
This is a 2021 ARVO Annual Meeting abstract.