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Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations

PURPOSE: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such sys...

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Autores principales: Patterson, Claire, Murphy, Dean, Irvine, Sarah, Connor, Leigh, Rattray, Zahra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225200/
https://www.ncbi.nlm.nih.gov/pubmed/32409985
http://dx.doi.org/10.1007/s11095-020-02825-9
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author Patterson, Claire
Murphy, Dean
Irvine, Sarah
Connor, Leigh
Rattray, Zahra
author_facet Patterson, Claire
Murphy, Dean
Irvine, Sarah
Connor, Leigh
Rattray, Zahra
author_sort Patterson, Claire
collection PubMed
description PURPOSE: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy. METHODS: Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray micro-computed tomography (μCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches. RESULTS: Our findings demonstrate that synchrotron μCT can be applied to the assessment of microsphere and vehicle distribution in s.c. tissue, and that microspheres can also be visualised in the absence of contrast agent using this approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time. CONCLUSIONS: The method outlined in this study provides a proof of concept feasibility for μCT application to determining the vehicle and suspended PLG microspheres fate following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-020-02825-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-72252002020-05-15 Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations Patterson, Claire Murphy, Dean Irvine, Sarah Connor, Leigh Rattray, Zahra Pharm Res Research Paper PURPOSE: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy. METHODS: Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray micro-computed tomography (μCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches. RESULTS: Our findings demonstrate that synchrotron μCT can be applied to the assessment of microsphere and vehicle distribution in s.c. tissue, and that microspheres can also be visualised in the absence of contrast agent using this approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time. CONCLUSIONS: The method outlined in this study provides a proof of concept feasibility for μCT application to determining the vehicle and suspended PLG microspheres fate following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-020-02825-9) contains supplementary material, which is available to authorized users. Springer US 2020-05-14 2020 /pmc/articles/PMC7225200/ /pubmed/32409985 http://dx.doi.org/10.1007/s11095-020-02825-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Paper
Patterson, Claire
Murphy, Dean
Irvine, Sarah
Connor, Leigh
Rattray, Zahra
Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations
title Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations
title_full Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations
title_fullStr Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations
title_full_unstemmed Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations
title_short Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations
title_sort novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225200/
https://www.ncbi.nlm.nih.gov/pubmed/32409985
http://dx.doi.org/10.1007/s11095-020-02825-9
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