Formulation and Characterization of Epalrestat-Loaded Polysorbate 60 Cationic Niosomes for Ocular Delivery

Abstract

The aim of this work was to develop niosomes for the ocular delivery of epalrestat, a drug that inhibits the polyol pathway and protects diabetic eyes from damage linked to sorbitol production and accumulation. Cationic niosomes were made using polysorbate 60, cholesterol, and 1,2-di-O-octadecenyl-3-trimethylammonium propane. The niosomes were characterized using dynamic light scattering, zeta-potential, and transmission electron microscopy to determine their size (80 nm; polydispersity index 0.3 to 0.5), charge (−23 to +40 mV), and shape (spherical). The encapsulation efficiency (99.76%) and the release (75% drug release over 20 days) were measured with dialysis. The ocular irritability potential (non-irritating) was measured using the Hen’s Egg Test on the Chorioallantoic Membrane model, and the blood glucose levels (on par with positive control) were measured using the gluc-HET model. The toxicity of the niosomes (non-toxic) was monitored using a zebrafish embryo model. Finally, corneal and scleral permeation was assessed with the help of Franz diffusion cells and confirmed with Raman spectroscopy. Niosomal permeation was higher than an unencapsulated drug in the sclera, and accumulation in tissues was confirmed with Raman. The prepared niosomes show promise to encapsulate and carry epalrestat through the eye to meet the need for controlled drug systems to treat the diabetic eye.

Langmuir monolayer studies of non-ionic surfactants and DOTMA for the design of ophthalmic niosomes

“…24 mN/m, at which the vesicles are thought to be [ 13 ]. This is compatible with the data published by our group [ 7 ] on the good stability of niosomes with this exact composition after two months.…”

“…All analyzed parameters confirm that cholesterol, at the mole fraction used for the formation of niosomes described in a previous article [ 7 ], while not having a particularly large effect in terms of mechanical changes to Langmuir films, gives rise to interactions with Tween 60 at the monolayer which influence the stability of the film.…”

“…To study the interaction between both components, mixed monolayers at a fixed composition ( Table 1 ) were spread and compressed. A Tween 60:cholesterol 70:30 mol/mol ratio was chosen since previous experiments evidenced that this content in cholesterol was the most adequate to form stable niosomes with Tween 60 [ 7 ]. This is in good agreement with π-A isotherms recorded for other nanocarriers in which amphiphilic components (DDAB and oleic acid) to cholesterol 5:2 M ratio [ 8 ] and monopalmitoyl glycerol plus dicetylphosphate to cholesterol 6:4 and 6:2 M ratios [ 22 ] were found as the optimal to render stable structures in aqueous medium.…”

“…3 ; where the higher concentration films contained twice as many molecules as the ones from the lower concentration. This duplicity of experiments for the ternary system, whose composition was set based on previous studies with niosomes [ 7 ], was necessary in order to investigate the molecular arrangement of these surfactants at a very wide range of surface pressure by obtaining isotherms as representative as possible.…”

“…They are made by allowing amphiphilic molecules to arrange inside an aqueous medium, while either encapsulating hydrophobic drugs in the micelle core or vesicle bilayer, or encapsulating hydrophilic drugs in the vesicle core. These structures, and niosomes in particular, have been recently studied by our research group in terms of particle characterization, drug encapsulation and eye tissue permeation [ 7 ]. However, there are still gaps in the understanding of the physical chemistry of the aggregation and interaction between the molecules that make up the nanocarrier.…”