Toxicity Evaluation of a Novel Rapamycin Liposomal Formulation After Subconjunctival and Intravitreal Injection

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

doi:10.1089/jop.2020.0108

Toxicity Evaluation of a Novel Rapamycin Liposomal Formulation After Subconjunctival and Intravitreal Injection

Journal

Journal of Ocular Pharmacology and Therapeutics

ISSN

1080-7683

1557-7732

Date Issued

2021

Author(s)

Salas-Ambrosio, Pedro Javier

Bernad-Bernad, María Josefa

Linares-Alba, Mónica Anayántzin

García-Santisteban, Rodrigo

Facultad de Ciencias de la Salud - CampCM

Tonix-Aburto, Luis Angel

Ornelas-Lobato, Guadalupe Jocelyn

Gracia-Mora, Isabel

Rivera-Huerta, Marisol

Sánchez-Bartez, Francisco

Rico-Morales, Héctor

García-Sánchez, Gustavo Adolfo

Type

text::journal::journal article

DOI

10.1089/jop.2020.0108

URL

https://scripta.up.edu.mx/handle/20.500.12552/2154

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.