Liposome assay for evaluating ocular toxicity of surfactants.
OBJECTIVE
The ocular toxicity of various compounds is typically determined by the Draize eye test, which has been criticized in the past for its lack of reproducibility and the cruelty associated with harsh testing conditions for animals. In this study, a liposome-based assay was developed for estimating ocular toxicity of surfactants.


METHODS
The release of calcein dye from liposomes induced by interactions with surfactants was studied and correlated to Draize eye scores. First, the liposome assay was conducted for various surfactants at identical concentrations and correlated to the Draize scores. Next, mechanistic and geometric considerations were used to determine the appropriate surfactant concentration that should be used in the liposome assay.


RESULTS
Correlations between the percentage of dye released and the Draize scores were drastically improved after surfactant concentrations were chosen based on CMC/200, where CMC is the critical micelle concentration of the surfactants. With this choice of surfactant concentration, excellent correlations were obtained with Draize scores from three separate sources and two different ocular surfactant loadings (Pearson = 0.99, 0.82, 0.78, and 0.74; Spearman = 0.94, 0.79, 0.79, and 0.85). Subsequently, the ocular toxicities of six nonionic surfactants, Brij 700, -58, -56, -78, -97, and -98 were shown to be minimal based on the proposed correlations.


CONCLUSIONS
The modified liposome assay developed in this study could be used in conjunction with other in vitro assays to obtain initial estimates for ocular toxicities and thus minimize the need for the Draize test.
Kapoor
Yash
Y
Department of Chemical Engineering, University of Florida, Gainesville, Florida 32611, USA.
Howell
Brett A
BA
Chauhan
Anuj
A
D003229:Conjunctival Diseases / Q000139:chemically induced; D003316:Corneal Diseases / Q000139:chemically induced; D003941:Diagnostic Techniques, Ophthalmological; D005452:Fluoresceins / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism*; D006801:Humans; D008081:Liposomes; D008163:Luminescent Measurements; D008962:Models, Theoretical; D010539:Permeability / Q000187:drug effects; D013501:Surface-Active Agents / Q000633:toxicity*
D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D013501:Surface-Active Agents; C007740:fluorexon