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Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector

PURPOSE: Methods of injection into the suprachoroidal space (SCS) have been developed for larger animals and humans, but reliable administration to the SCS of rodents remains challenging given their substantially smaller eyes. Here, we developed microneedle (MN)-based injectors for SCS delivery in r...

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Autores principales: Hejri, Amir, Bowland, Isabella I., Nickerson, John M., Prausnitz, Mark R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067776/
https://www.ncbi.nlm.nih.gov/pubmed/36995283
http://dx.doi.org/10.1167/tvst.12.3.31
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author Hejri, Amir
Bowland, Isabella I.
Nickerson, John M.
Prausnitz, Mark R.
author_facet Hejri, Amir
Bowland, Isabella I.
Nickerson, John M.
Prausnitz, Mark R.
author_sort Hejri, Amir
collection PubMed
description PURPOSE: Methods of injection into the suprachoroidal space (SCS) have been developed for larger animals and humans, but reliable administration to the SCS of rodents remains challenging given their substantially smaller eyes. Here, we developed microneedle (MN)-based injectors for SCS delivery in rats and guinea pigs. METHODS: We optimized key design features, including MN size and tip characteristics, MN hub design, and eye stabilization, to maximize injection reliability. Performance of the injection technique was characterized in rats (n = 13) and guinea pigs (n = 3) in vivo using fundoscopy and histological examinations to validate targeted SCS delivery. RESULTS: To enable SCS injection across the thin rodent sclera, the injector featured an ultrasmall, hollow MN measuring 160 µm in length for rats and 260 µm for guinea pigs. To control MN interaction with the scleral surface, we incorporated a three-dimensional (3D) printed needle hub to restrict scleral deformation at the injection site. A MN tip outer diameter of 110 µm and bevel angle of 55° optimized insertion without leakage. Additionally, a 3D printed probe was used to secure the eye by applying gentle vacuum. Injection by this technique took 1 minute to perform, was conducted without an operating microscope, and yielded a 100% success rate (19 of 19) of SCS delivery determined by fundoscopy and histology. A 7-day safety study revealed no notable adverse ocular effects. CONCLUSIONS: We conclude that this simple, targeted, and minimally invasive injection technique can enable SCS injection in rats and guinea pigs. TRANSLATIONAL RELEVANCE: This MN injector for rats and guinea pigs will expand and expedite preclinical investigations involving SCS delivery.
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spelling pubmed-100677762023-04-04 Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector Hejri, Amir Bowland, Isabella I. Nickerson, John M. Prausnitz, Mark R. Transl Vis Sci Technol Retina PURPOSE: Methods of injection into the suprachoroidal space (SCS) have been developed for larger animals and humans, but reliable administration to the SCS of rodents remains challenging given their substantially smaller eyes. Here, we developed microneedle (MN)-based injectors for SCS delivery in rats and guinea pigs. METHODS: We optimized key design features, including MN size and tip characteristics, MN hub design, and eye stabilization, to maximize injection reliability. Performance of the injection technique was characterized in rats (n = 13) and guinea pigs (n = 3) in vivo using fundoscopy and histological examinations to validate targeted SCS delivery. RESULTS: To enable SCS injection across the thin rodent sclera, the injector featured an ultrasmall, hollow MN measuring 160 µm in length for rats and 260 µm for guinea pigs. To control MN interaction with the scleral surface, we incorporated a three-dimensional (3D) printed needle hub to restrict scleral deformation at the injection site. A MN tip outer diameter of 110 µm and bevel angle of 55° optimized insertion without leakage. Additionally, a 3D printed probe was used to secure the eye by applying gentle vacuum. Injection by this technique took 1 minute to perform, was conducted without an operating microscope, and yielded a 100% success rate (19 of 19) of SCS delivery determined by fundoscopy and histology. A 7-day safety study revealed no notable adverse ocular effects. CONCLUSIONS: We conclude that this simple, targeted, and minimally invasive injection technique can enable SCS injection in rats and guinea pigs. TRANSLATIONAL RELEVANCE: This MN injector for rats and guinea pigs will expand and expedite preclinical investigations involving SCS delivery. The Association for Research in Vision and Ophthalmology 2023-03-30 /pmc/articles/PMC10067776/ /pubmed/36995283 http://dx.doi.org/10.1167/tvst.12.3.31 Text en Copyright 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Retina
Hejri, Amir
Bowland, Isabella I.
Nickerson, John M.
Prausnitz, Mark R.
Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector
title Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector
title_full Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector
title_fullStr Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector
title_full_unstemmed Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector
title_short Suprachoroidal Delivery in Rats and Guinea Pigs Using a High-Precision Microneedle Injector
title_sort suprachoroidal delivery in rats and guinea pigs using a high-precision microneedle injector
topic Retina
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067776/
https://www.ncbi.nlm.nih.gov/pubmed/36995283
http://dx.doi.org/10.1167/tvst.12.3.31
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