Dataset Information

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 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.

SUBMITTER: Lambert E

PROVIDER: S-EPMC7946885 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Lambert Eric E Janjic Jelena M JM

Scientific reports 20210310 1

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, desi ...[more]

PMID: 33692373

Similar Datasets

Project description:The ability to identify metabolically active and potentially salvageable ischaemic penumbra is crucial for improving treatment decisions in acute stroke patients. Our solution involves two complementary novel MRI techniques (Glasgow Oxygen Level Dependant (GOLD) Metabolic Imaging), which when combined with a perfluorocarbon (PFC) based oxygen carrier and hyperoxia can identify penumbra due to dynamic changes related to continued metabolism within this tissue compartment. Our aims were (i) to investigate whether PFC offers similar enhancement of the second technique (Lactate Change) as previously demonstrated for the T2*OC technique (ii) to demonstrate both GOLD metabolic imaging techniques working concurrently to identify penumbra, following administration of Oxycyte® (O-PFC) with hyperoxia. Methods: An established rat stroke model was utilised. Part-1: Following either saline or PFC, magnetic resonance spectroscopy was applied to investigate the effect of hyperoxia on lactate change in presumed penumbra. Part-2; rats received O-PFC prior to T2*OC (technique 1) and MR spectroscopic imaging, which was used to identify regions of tissue lactate change (technique 2) in response to hyperoxia. In order to validate the techniques, imaging was followed by [14C]2-deoxyglucose autoradiography to correlate tissue metabolic status to areas identified as penumbra. Results: Part-1: PFC+hyperoxia resulted in an enhanced reduction of lactate in the penumbra when compared to saline+hyperoxia. Part-2: Regions of brain tissue identified as potential penumbra by both GOLD metabolic imaging techniques utilising O-PFC, demonstrated maintained glucose metabolism as compared to adjacent core tissue. Conclusion: For the first time in vivo, enhancement of both GOLD metabolic imaging techniques has been demonstrated following intravenous O-PFC+hyperoxia to identify ischaemic penumbra. We have also presented preliminary evidence of the potential therapeutic benefit offered by O-PFC. These unique theranostic applications would enable treatment based on metabolic status of the brain tissue, independent of time from stroke onset, leading to increased uptake and safer use of currently available treatment options.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets