Quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers

Abstract Perfluorocarbons (PFCs) exhibiting high solubility for oxygen are attractive materials as artificial oxygen carriers (AOC), an alternative to whole blood or Haemoglobin-based oxygen carriers (HBOCs). PFC-based AOCs, however, met clinical translation roadblocks due to product quality control...

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Autores principales:	Eric Lambert, Jelena M. Janjic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f49e60f062294d3e8aabe71f7d9e7df1
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spelling	oai:doaj.org-article:f49e60f062294d3e8aabe71f7d9e7df12021-12-02T13:19:21ZQuality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers10.1038/s41598-021-84076-12045-2322https://doaj.org/article/f49e60f062294d3e8aabe71f7d9e7df12021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84076-1https://doaj.org/toc/2045-2322Abstract Perfluorocarbons (PFCs) exhibiting high solubility for oxygen are attractive materials as artificial oxygen carriers (AOC), an alternative to whole blood or Haemoglobin-based oxygen carriers (HBOCs). PFC-based AOCs, however, met clinical translation roadblocks due to product quality control challenges. To overcome these issues, we present an adaptation of Quality by Design (QbD) practices to optimization of PFC nanoemulsions (PFC-NEs) as AOCs. QbD elements including quality risk management, design of experiments (DoE), and multivariate data analysis facilitated the identification of composition and process parameters that strongly impacted PFC colloidal stability and oxygen transport function. Resulting quantitative relationships indicated a composition-driven tradeoff between stability and oxygen transport. It was found that PFC content was most predictive of in vitro oxygen release, but the PFC type (perfluoro-15-crown-5-ether, PCE or perfluorooctyl bromide, PFOB) had no effect on oxygen release. Furthermore, we found, under constant processing conditions, all PFC-NEs, comprised of varied PFC and hydrocarbon content, exhibited narrow droplet size range (100–150 nm) and narrow size distribution. Representative PFOB-NE maintained colloidal attributes upon manufacturing on larger scale (100 mL). QbD approach offers unique insights into PFC AOC performance, which will overcome current product development challenges and accelerate clinical translation.Eric LambertJelena M. JanjicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eric Lambert Jelena M. Janjic Quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers
description	Abstract Perfluorocarbons (PFCs) exhibiting high solubility for oxygen are attractive materials as artificial oxygen carriers (AOC), an alternative to whole blood or Haemoglobin-based oxygen carriers (HBOCs). PFC-based AOCs, however, met clinical translation roadblocks due to product quality control challenges. To overcome these issues, we present an adaptation of Quality by Design (QbD) practices to optimization of PFC nanoemulsions (PFC-NEs) as AOCs. QbD elements including quality risk management, design of experiments (DoE), and multivariate data analysis facilitated the identification of composition and process parameters that strongly impacted PFC colloidal stability and oxygen transport function. Resulting quantitative relationships indicated a composition-driven tradeoff between stability and oxygen transport. It was found that PFC content was most predictive of in vitro oxygen release, but the PFC type (perfluoro-15-crown-5-ether, PCE or perfluorooctyl bromide, PFOB) had no effect on oxygen release. Furthermore, we found, under constant processing conditions, all PFC-NEs, comprised of varied PFC and hydrocarbon content, exhibited narrow droplet size range (100–150 nm) and narrow size distribution. Representative PFOB-NE maintained colloidal attributes upon manufacturing on larger scale (100 mL). QbD approach offers unique insights into PFC AOC performance, which will overcome current product development challenges and accelerate clinical translation.
format	article
author	Eric Lambert Jelena M. Janjic
author_facet	Eric Lambert Jelena M. Janjic
author_sort	Eric Lambert
title	Quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers
title_short	Quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers
title_full	Quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers
title_fullStr	Quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers
title_full_unstemmed	Quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers
title_sort	quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f49e60f062294d3e8aabe71f7d9e7df1
work_keys_str_mv	AT ericlambert qualitybydesignapproachidentifiescriticalparametersdrivingoxygendeliveryperformanceinvitroforperfluorocarbonbasedartificialoxygencarriers AT jelenamjanjic qualitybydesignapproachidentifiescriticalparametersdrivingoxygendeliveryperformanceinvitroforperfluorocarbonbasedartificialoxygencarriers
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Quality by design approach identifies critical parameters driving oxygen delivery performance in vitro for perfluorocarbon based artificial oxygen carriers

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