Impact of the structure of phospholipid dispersions on the stability of fluorocarbon/phospholipid emulsions for biomedical uses

Cornelus, Chantal; Giulieri, Françoise; Riess, Marie-Pierre Krafft auJean G.

doi:10.1016/0927-7757(93)80297-r

Cited by 16 publications

(13 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to previously published data, although bromination of the fluorinated molecule can increase the inherent lipophilicity of the PFC, the mean size of the prepared emulsion still significantly increased after long-term storage 75-77. It is possible to increase stability by adding perfluorodecyl bromide (PFDB), a fluorocarbon-hydrocarbon diblock compound, to the PFOB core to reduce Ostwald ripening, the primary cause of the emulsion destabilization during long-term storage 27.…”

Section: Resultssupporting

confidence: 79%

Perfluorocarbon nanodroplets can reoxygenate hypoxic tumors in vivo without carbogen breathing

Yun¹,

Bernards²,

Hoang³

et al. 2019

Nanotheranostics

View full text Add to dashboard Cite

Nanoscale perfluorocarbon (PFC) droplets have enormous potential as clinical theranostic agents. They are biocompatible and are currently used in vivo as contrast agents for a variety of medical imaging modalities, including ultrasound, computed tomography, photoacoustic and 19 F-magnetic resonance imaging. PFC nanodroplets can also carry molecular and nanoparticulate drugs and be activated in situ by ultrasound or light for targeted therapy. Recently, there has been renewed interest in using PFC nanodroplets for hypoxic tumor reoxygenation towards radiosensitization based on the high oxygen solubility of PFCs. Previous studies showed that tumor oxygenation using PFC agents only occurs in combination with enhanced oxygen breathing. However, recent studies suggest that PFC agents that accumulate in solid tumors can contribute to radiosensitization, presumably due to tumor reoxygenation without enhanced oxygen breathing. In this study, we quantify the impact of oxygenation due to PFC nanodroplet accumulation in tumors alone in comparison with other reoxygenation methodologies, in particular, carbogen breathing. Methods: Lipid-stabilized, PFC (i.e., perfluorooctyl bromide, CF 3 (CF 2 ) 7 Br, PFOB) nanoscale droplets were synthesized and evaluated in xenograft prostate (DU145) tumors in male mice. Biodistribution assessment of the nanodroplets was achieved using a fluorescent lipophilic indocarbocyanine dye label (i.e., DiI dye) on the lipid shell in combination with fluorescence imaging in mice (n≥3 per group). Hypoxia reduction in tumors was measured using PET imaging and a known hypoxia radiotracer, [ 18 F]FAZA (n≥ 3 per group). Results: Lipid-stabilized nanoscale PFOB emulsions (mean diameter of ~250 nm), accumulated in the xenograft prostate tumors in mice 24 hours post-injection. In vivo PET imaging with [ 18 F]FAZA showed that the accumulation of the PFOB nanodroplets in the tumor tissues alone significantly reduced tumor hypoxia, without enhanced oxygen (i.e., carbogen) breathing. This reoxygenation effect was found to be comparable with carbogen breathing alone. Conclusion: Accumulation of nanoscale PFOB agents in solid tumors alone successfully reoxygenated hypoxic tumors to levels comparable with carbogen breathing alone, an established tumor oxygenation method. This study confirms that PFC agents can be used to reoxygenate hypoxic tumors in addition to their current applications as multifunctional theranostic agents.

show abstract

Section: Resultssupporting

confidence: 79%

Perfluorocarbon nanodroplets can reoxygenate hypoxic tumors in vivo without carbogen breathing

Yun¹,

Bernards²,

Hoang³

et al. 2019

Nanotheranostics

View full text Add to dashboard Cite

show abstract

“…It was argued that more molecules of oil are present within the interfacial boundary when PE and PS are used as emulsifiers which enhances droplet coalescence. Cornelus et al studied the effect of PL structure in the bulk phase on the stability of highly concentrated o/w emulsions [85]. Lecithin was dispersed in fluorocarbon in various manners to obtain three different structures: PC aggregates as “pre-liposomes”, multilayer liposomes (MLV) and small unilamellar vesicles (SUV).…”

Section: Applicationsmentioning

confidence: 99%

Phospholipids at the Interface: Current Trends and Challenges

Pichot

Watson

Norton

2013

IJMS

190

113

View full text Add to dashboard Cite

Phospholipids are one of the major structural elements of biological membranes. Due to their amphiphilic character, they can adopt various molecular assemblies when dispersed in water, such as bilayer vesicles or micelles, which give them unique interfacial properties and render them very attractive in terms of foam or emulsion stabilization. This article aims at reviewing the properties of phospholipids at the air/water and oil/water interfaces, as well as the recent advances in using these natural components as stabilizers, alone or in combination with other compounds such as proteins. A discussion regarding the challenges and opportunities offered by phospholipids-stabilized structure concludes the review.

show abstract

“…Though for example PLGA [ 23 , 24 ] or poloxamer [ 25 ] might be employed as well, the most often used emulsifiers are phospholipids [ 26 ]. For simple reasons, as phospholipids are well tolerated natural compounds approved for intravenous administration [ 27 ]. The formation of PFC-NE needs high energy input, which can be attained by means of high pressure homogenization or microfluidization [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Monitoring the Stability of Perfluorocarbon Nanoemulsions by Cryo-TEM Image Analysis and Dynamic Light Scattering

2015

View full text Add to dashboard Cite

Perfluorocarbon nanoemulsions (PFC-NE) are disperse systems consisting of nanoscale liquid perfluorocarbon droplets stabilized by an emulsifier, usually phospholipids. Perfluorocarbons are chemically inert and non-toxic substances that are exhaled after in vivo administration. The manufacture of PFC-NE can be done in large scales by means of high pressure homogenization or microfluidization. Originally investigated as oxygen carriers for cases of severe blood loss, their application nowadays is more focused on using them as marker agents in 19F Magnetic Resonance Imaging (19F MRI). 19F is scarce in organisms and thus PFC-NE are a promising tool for highly specific and non-invasive imaging of inflammation via 19F MRI. Neutrophils, monocytes and macrophages phagocytize PFC-NE and subsequently migrate to inflamed tissues. This technique has proven feasibility in numerous disease models in mice, rabbits and mini pigs. The translation to clinical trials in human needs the development of a stable nanoemulsion whose droplet size is well characterized over a long storage time. Usually dynamic light scattering (DLS) is applied as the standard method for determining particle sizes in the nanometer range. Our study uses a second method, analysis of transmission electron microscopy images of cryo-fixed samples (Cryo-TEM), to evaluate stability of PFC-NE in comparison to DLS. Four nanoemulsions of different composition are observed for one year. The results indicate that DLS alone cannot reveal the changes in particle size, but can even mislead to a positive estimation of stability. The combination with Cryo-TEM images gives more insight in the particulate evolution, both techniques supporting one another. The study is one further step in the development of analytical tools for the evaluation of a clinically applicable perfluorooctylbromide nanoemulsion.

show abstract

Impact of the structure of phospholipid dispersions on the stability of fluorocarbon/phospholipid emulsions for biomedical uses

Cited by 16 publications

References 7 publications

Perfluorocarbon nanodroplets can reoxygenate hypoxic tumors in vivo without carbogen breathing

Perfluorocarbon nanodroplets can reoxygenate hypoxic tumors in vivo without carbogen breathing

Phospholipids at the Interface: Current Trends and Challenges

Monitoring the Stability of Perfluorocarbon Nanoemulsions by Cryo-TEM Image Analysis and Dynamic Light Scattering

Contact Info

Product

Resources

About