Back to Search
Start Over
Toxicity Evaluation of a Novel Rapamycin Liposomal Formulation After Subconjunctival and Intravitreal Injection.
- Source :
-
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics [J Ocul Pharmacol Ther] 2021 Jun; Vol. 37 (5), pp. 261-276. Date of Electronic Publication: 2021 Mar 10. - Publication Year :
- 2021
-
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 :
- Animals
Chorioallantoic Membrane metabolism
Conjunctiva metabolism
Disease Models, Animal
Drug Compounding
Electroretinography methods
Erythrocytes drug effects
Erythrocytes metabolism
Immunosuppressive Agents administration & dosage
Immunosuppressive Agents toxicity
Intravitreal Injections
Liposomes administration & dosage
Liposomes therapeutic use
Male
Mice
Micronucleus Tests
Rabbits
Retina drug effects
Retina physiopathology
Safety
Sirolimus administration & dosage
Sirolimus toxicity
Autoimmune Diseases drug therapy
Eye Diseases immunology
Immunosuppressive Agents pharmacokinetics
Liposomes pharmacokinetics
Sirolimus pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7732
- Volume :
- 37
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 33691483
- Full Text :
- https://doi.org/10.1089/jop.2020.0108