Cargando…

Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina

PURPOSE: To compare ocular pharmacokinetics (PK), systemic absorption, and injectability of triamcinolone acetonide (TA) suprachoroidal (SC) and intravitreal (IVT) suspensions. METHODS: New Zealand White (NZW) rabbits received a bilateral injection of 4 mg TA injectable suspension, TRI (TRIESENCE (®...

Descripción completa

Detalles Bibliográficos
Autores principales: Muya, Leroy, Kansara, Viral, Cavet, Megan E., Ciulla, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9398478/
https://www.ncbi.nlm.nih.gov/pubmed/35404132
http://dx.doi.org/10.1089/jop.2021.0090
_version_ 1784772335984705536
author Muya, Leroy
Kansara, Viral
Cavet, Megan E.
Ciulla, Thomas
author_facet Muya, Leroy
Kansara, Viral
Cavet, Megan E.
Ciulla, Thomas
author_sort Muya, Leroy
collection PubMed
description PURPOSE: To compare ocular pharmacokinetics (PK), systemic absorption, and injectability of triamcinolone acetonide (TA) suprachoroidal (SC) and intravitreal (IVT) suspensions. METHODS: New Zealand White (NZW) rabbits received a bilateral injection of 4 mg TA injectable suspension, TRI (TRIESENCE (®); Alcon) through either microneedle-based SC or standard IVT injection. Another group of NZW rabbits received a bilateral SC injection (4 mg) of either TRI or a proprietary TA suspension for SC use, CLS-TA (Clearside Biomedical). Blood and ocular tissues were analyzed for TA over 3 months. Separately, injectability of TRI and CLS-TA through a proprietary SC delivery system (SCS Microinjector(®); Clearside Biomedical) was compared using microinjector syringe-plunger glide force measurement. RESULTS: Suprachoroidal delivery of TRI, compared with IVT-TRI, resulted in ∼12-fold higher exposure in the retinal pigment epithelium–choroid–sclera, and comparable exposure in the retina. Conversely, SC-TRI, compared to IVT-TRI, resulted in 460-, 34-, and 22-fold lower exposure in the lens, iris-ciliary body, and vitreous humor, and negligible exposure in the aqueous humor. SC injection of either CLS-TA or TRI resulted in comparable and sustained ocular TA levels. Plasma TA levels were generally undetectable in both studies. A significantly greater and more variable glide force was measured for TRI vs. CLS-TA. CONCLUSIONS: Suprachoroidal delivery of TA enabled high and durable TA levels targeted to the chorioretina with limited anterior segment exposure. SC delivery of either CLS-TA or TRI resulted in comparable ocular PK profiles with low systemic exposure; however, CLS-TA required lower and less variable glide force than TRI, potentiating more consistent, controlled administration.
format Online
Article
Text
id pubmed-9398478
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Mary Ann Liebert, Inc., publishers
record_format MEDLINE/PubMed
spelling pubmed-93984782022-08-24 Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina Muya, Leroy Kansara, Viral Cavet, Megan E. Ciulla, Thomas J Ocul Pharmacol Ther Original Articles PURPOSE: To compare ocular pharmacokinetics (PK), systemic absorption, and injectability of triamcinolone acetonide (TA) suprachoroidal (SC) and intravitreal (IVT) suspensions. METHODS: New Zealand White (NZW) rabbits received a bilateral injection of 4 mg TA injectable suspension, TRI (TRIESENCE (®); Alcon) through either microneedle-based SC or standard IVT injection. Another group of NZW rabbits received a bilateral SC injection (4 mg) of either TRI or a proprietary TA suspension for SC use, CLS-TA (Clearside Biomedical). Blood and ocular tissues were analyzed for TA over 3 months. Separately, injectability of TRI and CLS-TA through a proprietary SC delivery system (SCS Microinjector(®); Clearside Biomedical) was compared using microinjector syringe-plunger glide force measurement. RESULTS: Suprachoroidal delivery of TRI, compared with IVT-TRI, resulted in ∼12-fold higher exposure in the retinal pigment epithelium–choroid–sclera, and comparable exposure in the retina. Conversely, SC-TRI, compared to IVT-TRI, resulted in 460-, 34-, and 22-fold lower exposure in the lens, iris-ciliary body, and vitreous humor, and negligible exposure in the aqueous humor. SC injection of either CLS-TA or TRI resulted in comparable and sustained ocular TA levels. Plasma TA levels were generally undetectable in both studies. A significantly greater and more variable glide force was measured for TRI vs. CLS-TA. CONCLUSIONS: Suprachoroidal delivery of TA enabled high and durable TA levels targeted to the chorioretina with limited anterior segment exposure. SC delivery of either CLS-TA or TRI resulted in comparable ocular PK profiles with low systemic exposure; however, CLS-TA required lower and less variable glide force than TRI, potentiating more consistent, controlled administration. Mary Ann Liebert, Inc., publishers 2022-08-01 2022-08-01 /pmc/articles/PMC9398478/ /pubmed/35404132 http://dx.doi.org/10.1089/jop.2021.0090 Text en © Leroy Muya et al. 2022; Published by Mary Ann Liebert, Inc. https://creativecommons.org/licenses/by/4.0/This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Muya, Leroy
Kansara, Viral
Cavet, Megan E.
Ciulla, Thomas
Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina
title Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina
title_full Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina
title_fullStr Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina
title_full_unstemmed Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina
title_short Suprachoroidal Injection of Triamcinolone Acetonide Suspension: Ocular Pharmacokinetics and Distribution in Rabbits Demonstrates High and Durable Levels in the Chorioretina
title_sort suprachoroidal injection of triamcinolone acetonide suspension: ocular pharmacokinetics and distribution in rabbits demonstrates high and durable levels in the chorioretina
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9398478/
https://www.ncbi.nlm.nih.gov/pubmed/35404132
http://dx.doi.org/10.1089/jop.2021.0090
work_keys_str_mv AT muyaleroy suprachoroidalinjectionoftriamcinoloneacetonidesuspensionocularpharmacokineticsanddistributioninrabbitsdemonstrateshighanddurablelevelsinthechorioretina
AT kansaraviral suprachoroidalinjectionoftriamcinoloneacetonidesuspensionocularpharmacokineticsanddistributioninrabbitsdemonstrateshighanddurablelevelsinthechorioretina
AT cavetmegane suprachoroidalinjectionoftriamcinoloneacetonidesuspensionocularpharmacokineticsanddistributioninrabbitsdemonstrateshighanddurablelevelsinthechorioretina
AT ciullathomas suprachoroidalinjectionoftriamcinoloneacetonidesuspensionocularpharmacokineticsanddistributioninrabbitsdemonstrateshighanddurablelevelsinthechorioretina