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Cell Labeling for 19F MRI: New and Improved Approach to Perfluorocarbon Nanoemulsion Design.

Patel SK, Williams J, Janjic JM - Biosensors (Basel) (2013)

Bottom Line: This in turn can decrease efficacy of excess nanoemulsion removal and reliability of the cell labeling in vitro.Further, stressors such as elevated temperature in the presence of cells, and centrifugation, did not affect the nanoemulsion droplet size and polydispersity.Detailed synthetic methodology and in vitro testing for these new PFC nanoemulsions is presented.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA. patels1@duq.edu.

ABSTRACT
This report describes novel perfluorocarbon (PFC) nanoemulsions designed to improve ex vivo cell labeling for 19F magnetic resonance imaging (MRI). 19F MRI is a powerful non-invasive technique for monitoring cells of the immune system in vivo, where cells are labeled ex vivo with PFC nanoemulsions in cell culture. The quality of 19F MRI is directly affected by the quality of ex vivo PFC cell labeling. When co-cultured with cells for longer periods of time, nanoemulsions tend to settle due to high specific weight of PFC oils (1.5-2.0 g/mL). This in turn can decrease efficacy of excess nanoemulsion removal and reliability of the cell labeling in vitro. To solve this problem, novel PFC nanoemulsions are reported which demonstrate lack of sedimentation and high stability under cell labeling conditions. They are monodisperse, have small droplet size (~130 nm) and low polydispersity (<0.15), show a single peak in the 19F nuclear magnetic resonance spectrum at -71.4 ppm and possess high fluorine content. The droplet size and polydispersity remained unchanged after 160 days of follow up at three temperatures (4, 25 and 37 °C). Further, stressors such as elevated temperature in the presence of cells, and centrifugation, did not affect the nanoemulsion droplet size and polydispersity. Detailed synthetic methodology and in vitro testing for these new PFC nanoemulsions is presented.

No MeSH data available.


Related in: MedlinePlus

(a) 19F NMR of C8-PFTE (neat); (b) C8-PFTE structure.
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biosensors-03-00341-f001: (a) 19F NMR of C8-PFTE (neat); (b) C8-PFTE structure.

Mentions: Here we report a new nanoemulsion designed for 19F MRI that is resistant to sedimentation, with long shelf life and high stability under typical cell labeling conditions (exposure to serum, salts and elevated temperature). The nanoemulsion is formulated using a natural oil, biologically inert non-ionic surfactants and a lipophilic PFC construct, perfluoro-tert-butyl ether, 1-((1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-yl)oxy)octane (C8-PFTE), Figure 1. Since nanoemulsions are kinetically stabilized rather than thermodynamically, they are expected to be more sensitive to mechanical, temperature and chemical stress [17]. During co-incubation with nanoemulsions, the cell culture media containing serum, nutrients, salts and cellular products can have destabilizing effects on the nanoemulsion. If the nanoemulsion destabilizes during co-incubation with cells, the presence of larger droplets formed by aggregation or Ostwald ripening [18] could become very difficult to remove as they would settle very fast with cells in culture. To address this problem, we formulated a PFC nanoemulsion with oil density close to that of water and tested the nanoemulsion stability against centrifugation and prolonged exposure to complete cell culture medium. Below we summarize our findings and offer a new design approach for 19F MRI agent development where the nanoemulsion integrity is sustained during prolonged storage and use. The removal of excess nanoemulsion post labeling is easy and cell labeling is highly efficient. To the best of our knowledge this is the first report to directly address PFC nanoemulsion colloidal properties and its effects on cell labeling for 19F MRI.


Cell Labeling for 19F MRI: New and Improved Approach to Perfluorocarbon Nanoemulsion Design.

Patel SK, Williams J, Janjic JM - Biosensors (Basel) (2013)

(a) 19F NMR of C8-PFTE (neat); (b) C8-PFTE structure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263580&req=5

biosensors-03-00341-f001: (a) 19F NMR of C8-PFTE (neat); (b) C8-PFTE structure.
Mentions: Here we report a new nanoemulsion designed for 19F MRI that is resistant to sedimentation, with long shelf life and high stability under typical cell labeling conditions (exposure to serum, salts and elevated temperature). The nanoemulsion is formulated using a natural oil, biologically inert non-ionic surfactants and a lipophilic PFC construct, perfluoro-tert-butyl ether, 1-((1,1,1,3,3,3-hexafluoro-2-(trifluoromethyl)propan-2-yl)oxy)octane (C8-PFTE), Figure 1. Since nanoemulsions are kinetically stabilized rather than thermodynamically, they are expected to be more sensitive to mechanical, temperature and chemical stress [17]. During co-incubation with nanoemulsions, the cell culture media containing serum, nutrients, salts and cellular products can have destabilizing effects on the nanoemulsion. If the nanoemulsion destabilizes during co-incubation with cells, the presence of larger droplets formed by aggregation or Ostwald ripening [18] could become very difficult to remove as they would settle very fast with cells in culture. To address this problem, we formulated a PFC nanoemulsion with oil density close to that of water and tested the nanoemulsion stability against centrifugation and prolonged exposure to complete cell culture medium. Below we summarize our findings and offer a new design approach for 19F MRI agent development where the nanoemulsion integrity is sustained during prolonged storage and use. The removal of excess nanoemulsion post labeling is easy and cell labeling is highly efficient. To the best of our knowledge this is the first report to directly address PFC nanoemulsion colloidal properties and its effects on cell labeling for 19F MRI.

Bottom Line: This in turn can decrease efficacy of excess nanoemulsion removal and reliability of the cell labeling in vitro.Further, stressors such as elevated temperature in the presence of cells, and centrifugation, did not affect the nanoemulsion droplet size and polydispersity.Detailed synthetic methodology and in vitro testing for these new PFC nanoemulsions is presented.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA. patels1@duq.edu.

ABSTRACT
This report describes novel perfluorocarbon (PFC) nanoemulsions designed to improve ex vivo cell labeling for 19F magnetic resonance imaging (MRI). 19F MRI is a powerful non-invasive technique for monitoring cells of the immune system in vivo, where cells are labeled ex vivo with PFC nanoemulsions in cell culture. The quality of 19F MRI is directly affected by the quality of ex vivo PFC cell labeling. When co-cultured with cells for longer periods of time, nanoemulsions tend to settle due to high specific weight of PFC oils (1.5-2.0 g/mL). This in turn can decrease efficacy of excess nanoemulsion removal and reliability of the cell labeling in vitro. To solve this problem, novel PFC nanoemulsions are reported which demonstrate lack of sedimentation and high stability under cell labeling conditions. They are monodisperse, have small droplet size (~130 nm) and low polydispersity (<0.15), show a single peak in the 19F nuclear magnetic resonance spectrum at -71.4 ppm and possess high fluorine content. The droplet size and polydispersity remained unchanged after 160 days of follow up at three temperatures (4, 25 and 37 °C). Further, stressors such as elevated temperature in the presence of cells, and centrifugation, did not affect the nanoemulsion droplet size and polydispersity. Detailed synthetic methodology and in vitro testing for these new PFC nanoemulsions is presented.

No MeSH data available.


Related in: MedlinePlus