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Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particula...

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Autores principales: Giardiello, Marco, Liptrott, Neill J., McDonald, Tom O., Moss, Darren, Siccardi, Marco, Martin, Phil, Smith, Darren, Gurjar, Rohan, Rannard, Steve P., Owen, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078733/
https://www.ncbi.nlm.nih.gov/pubmed/27767027
http://dx.doi.org/10.1038/ncomms13184
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author Giardiello, Marco
Liptrott, Neill J.
McDonald, Tom O.
Moss, Darren
Siccardi, Marco
Martin, Phil
Smith, Darren
Gurjar, Rohan
Rannard, Steve P.
Owen, Andrew
author_facet Giardiello, Marco
Liptrott, Neill J.
McDonald, Tom O.
Moss, Darren
Siccardi, Marco
Martin, Phil
Smith, Darren
Gurjar, Rohan
Rannard, Steve P.
Owen, Andrew
author_sort Giardiello, Marco
collection PubMed
description Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.
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spelling pubmed-50787332016-11-02 Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies Giardiello, Marco Liptrott, Neill J. McDonald, Tom O. Moss, Darren Siccardi, Marco Martin, Phil Smith, Darren Gurjar, Rohan Rannard, Steve P. Owen, Andrew Nat Commun Article Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes. Nature Publishing Group 2016-10-21 /pmc/articles/PMC5078733/ /pubmed/27767027 http://dx.doi.org/10.1038/ncomms13184 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Giardiello, Marco
Liptrott, Neill J.
McDonald, Tom O.
Moss, Darren
Siccardi, Marco
Martin, Phil
Smith, Darren
Gurjar, Rohan
Rannard, Steve P.
Owen, Andrew
Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies
title Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies
title_full Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies
title_fullStr Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies
title_full_unstemmed Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies
title_short Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies
title_sort accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric hiv nanotherapies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078733/
https://www.ncbi.nlm.nih.gov/pubmed/27767027
http://dx.doi.org/10.1038/ncomms13184
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