Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics
© 2019 Elsevier B.V. Paclitaxel coated balloons (PCBs) are a promising non-implantable alternative to drug-eluting stents, whereby drug is delivered to the arterial wall in solid form as a semi-continuous solid coating or as micro drug depots. To date, it has been impossible to predict or even infer...
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| Format: | Article |
| Language: | English |
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Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/132384 |
| _version_ | 1826188608736854016 |
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| author | Tzafriri, Abraham R Parikh, Sahil A Edelman, Elazer R |
| author_facet | Tzafriri, Abraham R Parikh, Sahil A Edelman, Elazer R |
| author_sort | Tzafriri, Abraham R |
| collection | MIT |
| description | © 2019 Elsevier B.V. Paclitaxel coated balloons (PCBs) are a promising non-implantable alternative to drug-eluting stents, whereby drug is delivered to the arterial wall in solid form as a semi-continuous solid coating or as micro drug depots. To date, it has been impossible to predict or even infer local tissue dosing levels and persistence, making it difficult to compare in vivo performance of different devices in healthy animals or to extrapolate such data to diseased human arteries. Here we derive and analyze a coupled reaction diffusion model that accounts for coating dissolution and tissue distribution, and predicts the concentration of dissolved drug in the tissue during and post dissolution. Time scale analysis and numerical simulations based on estimated diffusion coefficients in healthy animal and diseased human arteries both imply that dissolution of crystalline paclitaxel coating is mass transfer coefficient-limited, and can therefore be solved for independently of the tissue transport equations. Specifically, coating retention is predicted to follow piecewise linear kinetics, reflecting the differential and faster dissolution of lumenal versus tissue-embedded coating owing to a disparity in convective forces. This prediction is consistent with published data on a range of PCBs and allowed for the estimation of the associated dissolution rate-constants and the maximal soluble drug concentration in the tissue during coating dissolution. Maximal soluble drug concentration in the tissue scales as the product of the solubility and ratio of the dissolution and diffusion rate-constants. Thus, coatings characterized by micromolar solubilities give rise to nanomolar soluble concentrations in healthy animal arteries and ~0.1 micromolar in calcified atherosclerotic arteries owing to slower tissue diffusion. During dissolution, retention in porcine iliofemoral arteries is predicted to be dominated by solid coating, whereas post dissolution it is dominated by receptor-bound drug (3.7 ng receptors/g tissue). Paclitaxel coating dissolution and dosing kinetics can now be modeled based upon accepted principles of surface dissolution and tissue transport to provide insights into the dependence of clinical efficacy on device properties and the interplay of lesion complexity and procedural parameters. |
| first_indexed | 2024-09-23T08:02:08Z |
| format | Article |
| id | mit-1721.1/132384 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:02:08Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1323842021-09-21T04:08:48Z Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics Tzafriri, Abraham R Parikh, Sahil A Edelman, Elazer R © 2019 Elsevier B.V. Paclitaxel coated balloons (PCBs) are a promising non-implantable alternative to drug-eluting stents, whereby drug is delivered to the arterial wall in solid form as a semi-continuous solid coating or as micro drug depots. To date, it has been impossible to predict or even infer local tissue dosing levels and persistence, making it difficult to compare in vivo performance of different devices in healthy animals or to extrapolate such data to diseased human arteries. Here we derive and analyze a coupled reaction diffusion model that accounts for coating dissolution and tissue distribution, and predicts the concentration of dissolved drug in the tissue during and post dissolution. Time scale analysis and numerical simulations based on estimated diffusion coefficients in healthy animal and diseased human arteries both imply that dissolution of crystalline paclitaxel coating is mass transfer coefficient-limited, and can therefore be solved for independently of the tissue transport equations. Specifically, coating retention is predicted to follow piecewise linear kinetics, reflecting the differential and faster dissolution of lumenal versus tissue-embedded coating owing to a disparity in convective forces. This prediction is consistent with published data on a range of PCBs and allowed for the estimation of the associated dissolution rate-constants and the maximal soluble drug concentration in the tissue during coating dissolution. Maximal soluble drug concentration in the tissue scales as the product of the solubility and ratio of the dissolution and diffusion rate-constants. Thus, coatings characterized by micromolar solubilities give rise to nanomolar soluble concentrations in healthy animal arteries and ~0.1 micromolar in calcified atherosclerotic arteries owing to slower tissue diffusion. During dissolution, retention in porcine iliofemoral arteries is predicted to be dominated by solid coating, whereas post dissolution it is dominated by receptor-bound drug (3.7 ng receptors/g tissue). Paclitaxel coating dissolution and dosing kinetics can now be modeled based upon accepted principles of surface dissolution and tissue transport to provide insights into the dependence of clinical efficacy on device properties and the interplay of lesion complexity and procedural parameters. 2021-09-20T18:22:08Z 2021-09-20T18:22:08Z 2020-10-19T13:53:49Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/132384 en 10.1016/J.JCONREL.2019.08.019 Journal of Controlled Release Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Tzafriri, Abraham R Parikh, Sahil A Edelman, Elazer R Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics |
| title | Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics |
| title_full | Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics |
| title_fullStr | Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics |
| title_full_unstemmed | Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics |
| title_short | Taking paclitaxel coated balloons to a higher level: Predicting coating dissolution kinetics, tissue retention and dosing dynamics |
| title_sort | taking paclitaxel coated balloons to a higher level predicting coating dissolution kinetics tissue retention and dosing dynamics |
| url | https://hdl.handle.net/1721.1/132384 |
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