Cargando…
Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection
PURPOSE: To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. METHODS: Suprachoroidal space collapse rate and pressure changes after microneedle injection into SCS were determined. Fluorescent fundus images were a...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283080/ https://www.ncbi.nlm.nih.gov/pubmed/28125841 http://dx.doi.org/10.1167/iovs.16-20679 |
_version_ | 1782503444709376000 |
---|---|
author | Chiang, Bryce Wang, Ke Ethier, C. Ross Prausnitz, Mark R. |
author_facet | Chiang, Bryce Wang, Ke Ethier, C. Ross Prausnitz, Mark R. |
author_sort | Chiang, Bryce |
collection | PubMed |
description | PURPOSE: To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. METHODS: Suprachoroidal space collapse rate and pressure changes after microneedle injection into SCS were determined. Fluorescent fundus images were acquired to determine clearance rates of molecules ranging in size from 332 Da to 2 MDa. Microneedle injections of fluorescein were performed, and samples were taken from various sites over time to determine amount of fluorescein exiting the eye. Clearance transport was modeled theoretically and compared with experimental data. RESULTS: After injection, pressures in SCS and vitreous humor spiked and returned to baseline within 20 minutes; there was no difference between these two pressures. Suprachoroidal space collapse occurred within 40 minutes. One hour after fluorescein injection, 46% of fluorescein was still present in the eye, 15% had transported across sclera, 6% had been cleared by choroidal vasculature, and 4% had exited via leakage pathways. Characteristic clearance time increased in proportion with molecular radius, but total clearance of 2 MDa FITC-dextran was significantly slower (21 days) than smaller molecules. These data generally agreed with predictions from a theoretical model of molecular transport. CONCLUSIONS: Guided by experimental data in the context of model predictions, molecular clearance from SCS occurred in three regimes: (1) on a time scale of approximately 10 minutes, fluid and molecules exited SCS by diffusion into sclera and choroid, and by pressure-driven reflux via transscleral leakage sites; (2) in approximately 1 hour, molecules cleared from choroid by blood flow; and (3) in 1 to 10 hours, molecules cleared from sclera by diffusion and convection. |
format | Online Article Text |
id | pubmed-5283080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-52830802017-02-01 Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection Chiang, Bryce Wang, Ke Ethier, C. Ross Prausnitz, Mark R. Invest Ophthalmol Vis Sci Physiology and Pharmacology PURPOSE: To determine clearance kinetics and routes of clearance of molecules from the suprachoroidal space (SCS) of live New Zealand White rabbits. METHODS: Suprachoroidal space collapse rate and pressure changes after microneedle injection into SCS were determined. Fluorescent fundus images were acquired to determine clearance rates of molecules ranging in size from 332 Da to 2 MDa. Microneedle injections of fluorescein were performed, and samples were taken from various sites over time to determine amount of fluorescein exiting the eye. Clearance transport was modeled theoretically and compared with experimental data. RESULTS: After injection, pressures in SCS and vitreous humor spiked and returned to baseline within 20 minutes; there was no difference between these two pressures. Suprachoroidal space collapse occurred within 40 minutes. One hour after fluorescein injection, 46% of fluorescein was still present in the eye, 15% had transported across sclera, 6% had been cleared by choroidal vasculature, and 4% had exited via leakage pathways. Characteristic clearance time increased in proportion with molecular radius, but total clearance of 2 MDa FITC-dextran was significantly slower (21 days) than smaller molecules. These data generally agreed with predictions from a theoretical model of molecular transport. CONCLUSIONS: Guided by experimental data in the context of model predictions, molecular clearance from SCS occurred in three regimes: (1) on a time scale of approximately 10 minutes, fluid and molecules exited SCS by diffusion into sclera and choroid, and by pressure-driven reflux via transscleral leakage sites; (2) in approximately 1 hour, molecules cleared from choroid by blood flow; and (3) in 1 to 10 hours, molecules cleared from sclera by diffusion and convection. The Association for Research in Vision and Ophthalmology 2017-01 /pmc/articles/PMC5283080/ /pubmed/28125841 http://dx.doi.org/10.1167/iovs.16-20679 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. |
spellingShingle | Physiology and Pharmacology Chiang, Bryce Wang, Ke Ethier, C. Ross Prausnitz, Mark R. Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection |
title | Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection |
title_full | Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection |
title_fullStr | Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection |
title_full_unstemmed | Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection |
title_short | Clearance Kinetics and Clearance Routes of Molecules From the Suprachoroidal Space After Microneedle Injection |
title_sort | clearance kinetics and clearance routes of molecules from the suprachoroidal space after microneedle injection |
topic | Physiology and Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283080/ https://www.ncbi.nlm.nih.gov/pubmed/28125841 http://dx.doi.org/10.1167/iovs.16-20679 |
work_keys_str_mv | AT chiangbryce clearancekineticsandclearanceroutesofmoleculesfromthesuprachoroidalspaceaftermicroneedleinjection AT wangke clearancekineticsandclearanceroutesofmoleculesfromthesuprachoroidalspaceaftermicroneedleinjection AT ethiercross clearancekineticsandclearanceroutesofmoleculesfromthesuprachoroidalspaceaftermicroneedleinjection AT prausnitzmarkr clearancekineticsandclearanceroutesofmoleculesfromthesuprachoroidalspaceaftermicroneedleinjection |