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Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles

Targeted drug and gene delivery using ultrasound and microbubbles (USMB) has the potential to treat several diseases. In vitro investigation of USMB-mediated delivery is of prime importance prior to in vivo studies because it is cost-efficient and allows for the rapid optimization of experimental pa...

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Autores principales: Joshi, Kushal, Sanwal, Rajiv, Thu, Kelsie L., Tsai, Scott S. H., Lee, Warren L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695114/
https://www.ncbi.nlm.nih.gov/pubmed/36432707
http://dx.doi.org/10.3390/pharmaceutics14112516
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author Joshi, Kushal
Sanwal, Rajiv
Thu, Kelsie L.
Tsai, Scott S. H.
Lee, Warren L.
author_facet Joshi, Kushal
Sanwal, Rajiv
Thu, Kelsie L.
Tsai, Scott S. H.
Lee, Warren L.
author_sort Joshi, Kushal
collection PubMed
description Targeted drug and gene delivery using ultrasound and microbubbles (USMB) has the potential to treat several diseases. In vitro investigation of USMB-mediated delivery is of prime importance prior to in vivo studies because it is cost-efficient and allows for the rapid optimization of experimental parameters. Most in vitro USMB studies are carried out with non-clinical, research-grade ultrasound systems, which are not approved for clinical use and are difficult to replicate by other labs. A standardized, low-cost, and easy-to-use in vitro experimental setup using a clinical ultrasound system would facilitate the eventual translation of the technology to the bedside. In this paper, we report a modular 3D-printed experimental setup using a clinical ultrasound transducer that can be used to study USMB-mediated drug delivery. We demonstrate its utility for optimizing various cargo delivery parameters in the HEK293 cell line, as well as for the CMT167 lung carcinoma cell line, using dextran as a model drug. We found that the proportion of dextran-positive cells increases with increasing mechanical index and ultrasound treatment time and decreases with increasing pulse interval (PI). We also observed that dextran delivery is most efficient for a narrow range of microbubble concentrations.
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spelling pubmed-96951142022-11-26 Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles Joshi, Kushal Sanwal, Rajiv Thu, Kelsie L. Tsai, Scott S. H. Lee, Warren L. Pharmaceutics Article Targeted drug and gene delivery using ultrasound and microbubbles (USMB) has the potential to treat several diseases. In vitro investigation of USMB-mediated delivery is of prime importance prior to in vivo studies because it is cost-efficient and allows for the rapid optimization of experimental parameters. Most in vitro USMB studies are carried out with non-clinical, research-grade ultrasound systems, which are not approved for clinical use and are difficult to replicate by other labs. A standardized, low-cost, and easy-to-use in vitro experimental setup using a clinical ultrasound system would facilitate the eventual translation of the technology to the bedside. In this paper, we report a modular 3D-printed experimental setup using a clinical ultrasound transducer that can be used to study USMB-mediated drug delivery. We demonstrate its utility for optimizing various cargo delivery parameters in the HEK293 cell line, as well as for the CMT167 lung carcinoma cell line, using dextran as a model drug. We found that the proportion of dextran-positive cells increases with increasing mechanical index and ultrasound treatment time and decreases with increasing pulse interval (PI). We also observed that dextran delivery is most efficient for a narrow range of microbubble concentrations. MDPI 2022-11-19 /pmc/articles/PMC9695114/ /pubmed/36432707 http://dx.doi.org/10.3390/pharmaceutics14112516 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Joshi, Kushal
Sanwal, Rajiv
Thu, Kelsie L.
Tsai, Scott S. H.
Lee, Warren L.
Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles
title Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles
title_full Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles
title_fullStr Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles
title_full_unstemmed Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles
title_short Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles
title_sort plug and pop: a 3d-printed, modular platform for drug delivery using clinical ultrasound and microbubbles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695114/
https://www.ncbi.nlm.nih.gov/pubmed/36432707
http://dx.doi.org/10.3390/pharmaceutics14112516
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