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Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up
One of the foremost challenges in translating nanoparticle technologies to the clinic is the requirement to produce materials on a large-scale. Scaling nanoparticle production methods is often non-trivial, and the success of these endeavors is frequently governed by whether or not an intermediate le...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489532/ https://www.ncbi.nlm.nih.gov/pubmed/34280414 http://dx.doi.org/10.1016/j.jconrel.2021.07.012 |
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author | Colby, Aaron H. Liu, Rong Doyle, Robert P. Merting, Alyssa Zhang, Heng Savage, Natasha Chu, Ngoc-Quynh Hollister, Beth A. McCulloch, William Burdette, Joanna E. Pearce, Cedric J. Liu, Kebin Oberlies, Nicholas H. Colson, Yolonda L. Grinstaff, Mark W. |
author_facet | Colby, Aaron H. Liu, Rong Doyle, Robert P. Merting, Alyssa Zhang, Heng Savage, Natasha Chu, Ngoc-Quynh Hollister, Beth A. McCulloch, William Burdette, Joanna E. Pearce, Cedric J. Liu, Kebin Oberlies, Nicholas H. Colson, Yolonda L. Grinstaff, Mark W. |
author_sort | Colby, Aaron H. |
collection | PubMed |
description | One of the foremost challenges in translating nanoparticle technologies to the clinic is the requirement to produce materials on a large-scale. Scaling nanoparticle production methods is often non-trivial, and the success of these endeavors is frequently governed by whether or not an intermediate level of production, i.e., “pilot-scale” production, can be achieved. Pilot-scale production at the one-liter scale serves as a proof-of-concept that large-scale production will be possible. Here, we describe the pilot-scale production of the expansile nanoparticle (eNP) technology including verification of activity and efficacy following scaleup. We describe the challenges of sonication-based emulsification procedures and how these were overcome by use of a Microfluidizer technology. We also describe the problem-solving process that led to pre-polymerization of the nanoparticle polymer—a fundamental change from the lab-scale and previously published methods. Furthermore, we demonstrate good control over particle diameter, polydispersity and drug loading and the ability to sterilize the particles via filtration using this method. To facilitate long-term storage of these larger quantities of particles, we investigated six lyoprotectants and determined that sucrose is the most compatible with the current system. Lastly, we demonstrate that these changes to the manufacturing method do not adversely affect the swelling functionality of the particles, their highly specific localization to tumors, their non-toxicity in vivo or their efficacy in treating established intraperitoneal mesothelioma xenografts. |
format | Online Article Text |
id | pubmed-8489532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-84895322021-10-04 Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up Colby, Aaron H. Liu, Rong Doyle, Robert P. Merting, Alyssa Zhang, Heng Savage, Natasha Chu, Ngoc-Quynh Hollister, Beth A. McCulloch, William Burdette, Joanna E. Pearce, Cedric J. Liu, Kebin Oberlies, Nicholas H. Colson, Yolonda L. Grinstaff, Mark W. J Control Release Article One of the foremost challenges in translating nanoparticle technologies to the clinic is the requirement to produce materials on a large-scale. Scaling nanoparticle production methods is often non-trivial, and the success of these endeavors is frequently governed by whether or not an intermediate level of production, i.e., “pilot-scale” production, can be achieved. Pilot-scale production at the one-liter scale serves as a proof-of-concept that large-scale production will be possible. Here, we describe the pilot-scale production of the expansile nanoparticle (eNP) technology including verification of activity and efficacy following scaleup. We describe the challenges of sonication-based emulsification procedures and how these were overcome by use of a Microfluidizer technology. We also describe the problem-solving process that led to pre-polymerization of the nanoparticle polymer—a fundamental change from the lab-scale and previously published methods. Furthermore, we demonstrate good control over particle diameter, polydispersity and drug loading and the ability to sterilize the particles via filtration using this method. To facilitate long-term storage of these larger quantities of particles, we investigated six lyoprotectants and determined that sucrose is the most compatible with the current system. Lastly, we demonstrate that these changes to the manufacturing method do not adversely affect the swelling functionality of the particles, their highly specific localization to tumors, their non-toxicity in vivo or their efficacy in treating established intraperitoneal mesothelioma xenografts. 2021-07-16 2021-09-10 /pmc/articles/PMC8489532/ /pubmed/34280414 http://dx.doi.org/10.1016/j.jconrel.2021.07.012 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ). |
spellingShingle | Article Colby, Aaron H. Liu, Rong Doyle, Robert P. Merting, Alyssa Zhang, Heng Savage, Natasha Chu, Ngoc-Quynh Hollister, Beth A. McCulloch, William Burdette, Joanna E. Pearce, Cedric J. Liu, Kebin Oberlies, Nicholas H. Colson, Yolonda L. Grinstaff, Mark W. Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up |
title | Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up |
title_full | Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up |
title_fullStr | Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up |
title_full_unstemmed | Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up |
title_short | Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up |
title_sort | pilot-scale production of expansile nanoparticles: practical methods for clinical scale-up |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489532/ https://www.ncbi.nlm.nih.gov/pubmed/34280414 http://dx.doi.org/10.1016/j.jconrel.2021.07.012 |
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