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- Title
Toxicity Evaluation of a Novel Rapamycin Liposomal Formulation After Subconjunctival and Intravitreal Injection.
- Authors
Salas-Ambrosio, Pedro Javier; Bernad-Bernad, María Josefa; Linares-Alba, Mónica Anayántzin; García-Santisteban, Rodrigo; Tonix-Aburto, Luis Angel; Ornelas-Lobato, Guadalupe Jocelyn; Gracia-Mora, Isabel; Rivera-Huerta, Marisol; Sánchez-Bartez, Francisco; Rico-Morales, Héctor; García-Sánchez, Gustavo Adolfo
- Abstract
Purpose: Safety and toxicity evaluation of a novel, liposome-encapsulated rapamycin formulation, intended for autoimmune ocular disorders. Methods: The formulation was assessed by micronucleus polychromatic erythrocyte production, irritability by Hen's Egg Test-Chorioallantoic Membrane (HET CAM), sterility, and pyrogenicity testing. Subconjunctival (SCJ) and intravitreal (IVT) administration of the formulation were performed to evaluate subacute and acute toxicity, respectively. Differences between groups in biochemical and hematological parameters were evaluated by analysis of variance and t-tests. Numeric score was assigned to histopathological classification. Electroretinography (ERG) testing was also performed. Data were analyzed by a 1 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 results were negative. Pathology demonstrated no damage related to the formulation after SCJ injection. After IVT injection, only lens injury associated with technique was observed. Retinal function was also conserved in ERG. Conclusions: The preparation evaluated offers a good toxicity and safety profile when injected in a SCJ or IVT 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.
- Subjects
INTRAVITREAL injections; LIPOSOMES; EGGS; INJECTIONS; HISTOPATHOLOGY; KRUSKAL-Wallis Test; RAPAMYCIN; ERYTHROCYTE metabolism; ARTIFICIAL membranes; SAFETY; BIOLOGICAL models; RESEARCH; RETINA; ANIMAL experimentation; AUTOIMMUNE diseases; RABBITS; EVALUATION research; CONJUNCTIVA; COMPARATIVE studies; RESEARCH funding; IMMUNOSUPPRESSIVE agents; ERYTHROCYTES; EYE diseases; ELECTRORETINOGRAPHY; DOSAGE forms of drugs; MICE
- Publication
Journal of Ocular Pharmacology & Therapeutics, 2021, Vol 37, Issue 5, p261
- ISSN
1080-7683
- Publication type
journal article
- DOI
10.1089/jop.2020.0108