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Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma
PURPOSE: We developed polycaprolactone (PCL) implants that achieve zero-order release of a proprietary ocular hypotensive agent (DE-117) over 6 months. METHODS: The release rates of DE-117–loaded PCL devices were tuned based on an established predictive model and confirmed by in vitro release studie...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Association for Research in Vision and Ophthalmology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015984/ https://www.ncbi.nlm.nih.gov/pubmed/27556217 http://dx.doi.org/10.1167/iovs.16-19585 |
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author | Kim, Jean Kudisch, Max Mudumba, Sri Asada, Hiroyuki Aya-Shibuya, Eri Bhisitkul, Robert B. Desai, Tejal A. |
author_facet | Kim, Jean Kudisch, Max Mudumba, Sri Asada, Hiroyuki Aya-Shibuya, Eri Bhisitkul, Robert B. Desai, Tejal A. |
author_sort | Kim, Jean |
collection | PubMed |
description | PURPOSE: We developed polycaprolactone (PCL) implants that achieve zero-order release of a proprietary ocular hypotensive agent (DE-117) over 6 months. METHODS: The release rates of DE-117–loaded PCL devices were tuned based on an established predictive model and confirmed by in vitro release studies. Devices containing DE-117 and empty devices were implanted intracamerally in normotensive rabbits for up to 8 weeks' duration. Devices were retrieved after rabbits were euthanized and evaluated for tissue adherence. The drug remaining in each device was analyzed by high performance liquid chromatography. Drug distribution in ocular tissues was measured by liquid chromatography coupled with a tandem mass spectrometry (LC/MS/MS). RESULTS: In vitro release of DE-117 showed zero-order release with a release rate of 0.5 μg/day over 6 months. Implantation in rabbit eyes demonstrated that the devices were well tolerated in the intracameral space. Quantification of DE-117 and hDE-117 (the hydrolyzed active form of DE-117) in ocular tissues (cornea, iris-ciliary body, aqueous humor, and vitreous humor) indicated sustained release of DE-117 and its conversion to hDE-117 when released from the device. Analysis of drug remaining in the device found that concentration of hDE-117 was below the limit of detection, indicating the encapsulated drug was protected from hydrolysis in the device. CONCLUSIONS: Proof-of-concept PCL drug delivery devices containing DE-117 show promise as a long-term glaucoma treatment based on their zero-order drug release profile in vitro, biocompatibility in vivo, and effective distribution of released drug in relevant ocular tissues. |
format | Online Article Text |
id | pubmed-5015984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Association for Research in Vision and Ophthalmology |
record_format | MEDLINE/PubMed |
spelling | pubmed-50159842016-09-09 Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma Kim, Jean Kudisch, Max Mudumba, Sri Asada, Hiroyuki Aya-Shibuya, Eri Bhisitkul, Robert B. Desai, Tejal A. Invest Ophthalmol Vis Sci Glaucoma PURPOSE: We developed polycaprolactone (PCL) implants that achieve zero-order release of a proprietary ocular hypotensive agent (DE-117) over 6 months. METHODS: The release rates of DE-117–loaded PCL devices were tuned based on an established predictive model and confirmed by in vitro release studies. Devices containing DE-117 and empty devices were implanted intracamerally in normotensive rabbits for up to 8 weeks' duration. Devices were retrieved after rabbits were euthanized and evaluated for tissue adherence. The drug remaining in each device was analyzed by high performance liquid chromatography. Drug distribution in ocular tissues was measured by liquid chromatography coupled with a tandem mass spectrometry (LC/MS/MS). RESULTS: In vitro release of DE-117 showed zero-order release with a release rate of 0.5 μg/day over 6 months. Implantation in rabbit eyes demonstrated that the devices were well tolerated in the intracameral space. Quantification of DE-117 and hDE-117 (the hydrolyzed active form of DE-117) in ocular tissues (cornea, iris-ciliary body, aqueous humor, and vitreous humor) indicated sustained release of DE-117 and its conversion to hDE-117 when released from the device. Analysis of drug remaining in the device found that concentration of hDE-117 was below the limit of detection, indicating the encapsulated drug was protected from hydrolysis in the device. CONCLUSIONS: Proof-of-concept PCL drug delivery devices containing DE-117 show promise as a long-term glaucoma treatment based on their zero-order drug release profile in vitro, biocompatibility in vivo, and effective distribution of released drug in relevant ocular tissues. The Association for Research in Vision and Ophthalmology 2016-08-24 2016-08 /pmc/articles/PMC5015984/ /pubmed/27556217 http://dx.doi.org/10.1167/iovs.16-19585 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 | Glaucoma Kim, Jean Kudisch, Max Mudumba, Sri Asada, Hiroyuki Aya-Shibuya, Eri Bhisitkul, Robert B. Desai, Tejal A. Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma |
title | Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma |
title_full | Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma |
title_fullStr | Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma |
title_full_unstemmed | Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma |
title_short | Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma |
title_sort | biocompatibility and pharmacokinetic analysis of an intracameral polycaprolactone drug delivery implant for glaucoma |
topic | Glaucoma |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015984/ https://www.ncbi.nlm.nih.gov/pubmed/27556217 http://dx.doi.org/10.1167/iovs.16-19585 |
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