Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution
In vitro prediction of physiologically relevant transport of therapeutic molecules across the microcirculation represents an intriguing opportunity to predict efficacy in human populations. On-chip microvascular networks (MVNs) show physiologically relevant values of molecular permeability, yet like...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020
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| Online Access: | https://hdl.handle.net/1721.1/128270 |
| _version_ | 1826195815561953280 |
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| author | Offeddu, Giovanni Possenti, Luca Loessberg‐Zahl, Joshua T Zunino, Paolo Roberts, John Han, Xiaogang Hickman, Dean Knutson, Charles G Kamm, Roger Dale |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Offeddu, Giovanni Possenti, Luca Loessberg‐Zahl, Joshua T Zunino, Paolo Roberts, John Han, Xiaogang Hickman, Dean Knutson, Charles G Kamm, Roger Dale |
| author_sort | Offeddu, Giovanni |
| collection | MIT |
| description | In vitro prediction of physiologically relevant transport of therapeutic molecules across the microcirculation represents an intriguing opportunity to predict efficacy in human populations. On-chip microvascular networks (MVNs) show physiologically relevant values of molecular permeability, yet like most systems, they lack an important contribution to transport: the ever-present fluid convection through the endothelium. Quantification of transport through the MVNs by current methods also requires confocal imaging and advanced analytical techniques, which can be a bottleneck in industry and academic laboratories. Here, it is shown that by recapitulating physiological transmural flow across the MVNs, the concentration of small and large molecule therapeutics can be directly sampled in the interstitial fluid and analyzed using standard analytical techniques. The magnitudes of transport measured in MVNs reveal trends with molecular size and type (protein versus nonprotein) that are expected in vivo, supporting the use of the MVNs platform as an in vitro tool to predict distribution of therapeutics in vivo. |
| first_indexed | 2024-09-23T10:15:55Z |
| format | Article |
| id | mit-1721.1/128270 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:15:55Z |
| publishDate | 2020 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1282702022-09-30T20:00:20Z Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution Offeddu, Giovanni Possenti, Luca Loessberg‐Zahl, Joshua T Zunino, Paolo Roberts, John Han, Xiaogang Hickman, Dean Knutson, Charles G Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering In vitro prediction of physiologically relevant transport of therapeutic molecules across the microcirculation represents an intriguing opportunity to predict efficacy in human populations. On-chip microvascular networks (MVNs) show physiologically relevant values of molecular permeability, yet like most systems, they lack an important contribution to transport: the ever-present fluid convection through the endothelium. Quantification of transport through the MVNs by current methods also requires confocal imaging and advanced analytical techniques, which can be a bottleneck in industry and academic laboratories. Here, it is shown that by recapitulating physiological transmural flow across the MVNs, the concentration of small and large molecule therapeutics can be directly sampled in the interstitial fluid and analyzed using standard analytical techniques. The magnitudes of transport measured in MVNs reveal trends with molecular size and type (protein versus nonprotein) that are expected in vivo, supporting the use of the MVNs platform as an in vitro tool to predict distribution of therapeutics in vivo. 2020-10-30T15:19:59Z 2020-10-30T15:19:59Z 2019-09 2019-08 2020-10-28T18:10:23Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/128270 Offeddu, Giovanni et al. "Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution." Small 15, 46 (November 2019): 1902393 © 2019 Wiley en http://dx.doi.org/10.1002/SMLL.201902393 Small Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Prof. Kamm via Elizabeth Soergel |
| spellingShingle | Offeddu, Giovanni Possenti, Luca Loessberg‐Zahl, Joshua T Zunino, Paolo Roberts, John Han, Xiaogang Hickman, Dean Knutson, Charles G Kamm, Roger Dale Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution |
| title | Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution |
| title_full | Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution |
| title_fullStr | Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution |
| title_full_unstemmed | Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution |
| title_short | Application of Transmural Flow Across In Vitro Microvasculature Enables Direct Sampling of Interstitial Therapeutic Molecule Distribution |
| title_sort | application of transmural flow across in vitro microvasculature enables direct sampling of interstitial therapeutic molecule distribution |
| url | https://hdl.handle.net/1721.1/128270 |
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