TOXICITY EVALUATION OF A NOVEL RAPAMYCIN LIPOSOMAL FORMULATION AFTER
SUBCONJUNCTIVAL AND INTRAVITREAL INJECTION
Purpose: Safety and toxicity evaluation of a nove liposome-encapsulated
rapamycin formulation, intended for autoimmune ocular disorders.
Methods: The formulation (60 and 180 µg for subconjunctival and 40 and
440 µg for intravitreal administration) were assessed through
micronucleus polychromatic erythrocytes production, and irritability by
HET CAM and pyrogenicity testing. Subconjunctival and intravitreal
administration of the formulation were performed to evaluate subacute
and acute toxicity, respectively. Shapiro Wilk and Kolmogorov-Smirnov
tests were applied for normality. Pearson and Spearman Correlation tests
for variable comparison. Differences between groups in biochemical and
hematological parameters were evaluated by ANOVA test with significance
determination by t-Holm-Sidak post-hoc test. A t-test was employed to
compare independent, normally distributed variables. Numeric score was
assigned to histopathological classification. Data was analyzed by a one
way no parametric Kruskal-Wallis and the Mann-Whitney tests.
Significance was considered when p<0.05 Results: No
significant toxicity directly related to the preparation was detected.
Micronucleus count, mucous irritation score, and pyrogenicity were
negative. Pathology demonstrated no damage related to the formulation
after subconjunctival injection. After intravitreal injection, only lens
injury associated with the technique was observed. Retinal function was
also conserved in electroretinography. (ERG). Conclusions: The
preparation evaluated offers a good toxicity and safety profile when
injected in a subconjunctival or intravitreal manner in an animal model.
A clinical trial conducted in humans is highly warranted, as it could
reveal an alternative immunosuppressive treatment for ophthalmological