loading page

TOXICITY EVALUATION OF A NOVEL RAPAMYCIN LIPOSOMAL FORMULATION AFTER SUBCONJUNCTIVAL AND INTRAVITREAL INJECTION
  • +8
  • Rodrigo Garcia-Santisteban,
  • María Josefa Bernad-Bernad,
  • Pedro Javier Salas Ambrosio,
  • Monica Linares-Alba,
  • Luis Tonix-Aburto,
  • Guadalupe Ornelas-Lobato,
  • Isabel Gracia-Mora,
  • Marisol Rivera-Huerta,
  • Francisco Sánchez-Bartez,
  • Héctor Rico-Morales,
  • Gustavo García-Sánchez
Rodrigo Garcia-Santisteban
Universidad Panamericana - Campus México
Author Profile
María Josefa Bernad-Bernad
Universidad Nacional Autonoma de Mexico
Author Profile
Pedro Javier Salas Ambrosio
Universidad Nacional Autonoma de Mexico
Author Profile
Monica Linares-Alba
Universidad Nacional Autonoma de Mexico
Author Profile
Luis Tonix-Aburto
Universidad Nacional Autonoma de Mexico
Author Profile
Guadalupe Ornelas-Lobato
Universidad Nacional Autonoma de Mexico
Author Profile
Isabel Gracia-Mora
Universidad Nacional Autonoma de Mexico
Author Profile
Marisol Rivera-Huerta
Universidad Nacional Autonoma de Mexico
Author Profile
Francisco Sánchez-Bartez
Universidad Nacional Autonoma de Mexico
Author Profile
Héctor Rico-Morales
Universidad Nacional Autonoma de Mexico
Author Profile
Gustavo García-Sánchez
Universidad Nacional Autonoma de Mexico
Author Profile

Abstract

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 immune-mediated pathologies.