Abstract
Purpose :
The increase of diabetic patients leads to an increase of ocular diabetic diseases as diabetic retinopathy. This occurs when the retina degrades due to osmotic pressure and oxidative stress caused by the polyol pathway, activated in high glycemic conditions. This pathway is blocked by epalrestat, a drug already used in the context of diabetic neuropathy, but the epalrestat molecule is very hydrophobic. It is hypothesized that the formation of a niosomal complex as a carrier for epalrestat will display physicochemical properties and have an encapsulation efficiency that points towards the molecule being able to reach the posterior segment of the eye, which is the therapeutic site.
Methods :
Formulation of the niosomes was done using different molar ratios of surfactant:helper lipid:charge modifier/Tween80:cholesterol:DOTMA. The reagents were dissolved in ethanol, dried with a rotavapor, then hydrated with MilliQ water. The flask was ultrasonicated, and then sonified with a probe sonifier. Dialysis was performed to remove unencapsulated drug. The niosomes formed were characterized in terms of size, polydispersity, surface charge and morphology using DLS, zeta-potential and TEM. Quantification of epalrestat in subsequent experiments was done by HPLC. The encapsulation efficiency and release profile were measured by dialysis, in 14 000 kDa cellulose tubing.
Results :
Loaded niosomes were formed with the physicochemical properties and encapsulation efficiency as described below. The morphology was spherical.
T60CD0ef: 84 nm, 0.541 PDI, -23.34 ± 5.341 mV zeta-potential, 99.86 ± 0.24% encapsulation efficiency.
T60CD5ef: 69 nm, 0.460 PDI, +17.27 ± 10.29 mV zeta-potential, 99.75 ± 0.35% encapsulation efficiency.
T60CD10ef: 75nm, 0.279 PDI, +40.39 ± 10.29 mV zeta-potential, 99.64 ± 0.13% encapsulation efficiency.
The release profile showed better release with lower DOTMA percentage, up until 10 days, when the niosomes with 5% DOTMA released more than niosomes without charge modifier. (Image 1)
Conclusions :
The hypothesis was confirmed and niosomal particles were prepared using a robust protocol. To confirm the viability of such particles tissue permeation experiments will be performed. The effect of surface charge on the ability of epalrestat to escape the niosomes should be explored in more detail.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.