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Optimization and characterization of stable lipid‐based, oxygen‐filled microbubbles by mixture design
Author(s) -
Polizzotti Brian D.,
Thomson Lindsay M.,
O'Connell Daniel W.,
McGowan Francis X.,
Kheir John N.
Publication year - 2014
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.33096
Subject(s) - dispersity , materials science , oxygen , microbubbles , biomedical engineering , excipient , chemical engineering , chromatography , organic chemistry , ultrasound , chemistry , polymer chemistry , medicine , engineering , radiology
Tissue hypoxia is a final common pathway that leads to cellular injury and death in a number of critical illnesses. Intravenous injections of self‐assembling, lipid‐based oxygen microbubbles (LOMs) can be used to deliver oxygen gas, preventing organ injury and death from systemic hypoxemia. However, current formulations exhibit high polydispersity indices (which may lead to microvascular obstruction) and poor shelf‐lives, limiting the translational capacity of LOMs. In this study, we report our efforts to optimize LOM formulations using a mixture response surface methodology (mRSM). We study the effect of changing excipient proportions (the independent variables) on microbubble diameter and product loss (the dependent variables). By using mRSM analysis, the experimental data were fit using a reduced Scheffé linear mixture model. We demonstrate that formulations manufactured from 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine, corn syrup, and water produce micron‐sized microbubbles with low polydispersity indices, and decreased product loss (relative to previously described formulations) when stored at room temperature over a 30‐day period. Optimized LOMs were subsequently tested for their oxygen‐releasing ability and found to have similar release kinetics as prior formulations. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1148–1156, 2014.