Preserving the Integrity of Surfactant-Stabilized Microbubble Membranes for Localized Oxygen Delivery
Ultrasound contrast agents consist of stabilized microbubbles. We are developing a surfactant-stabilized microbubble platform with a shell composed of Span 60 (Sorbitan monostearate) and an emulsifying agent, water-soluble vitamin E (α-tocopheryl poly(ethylene glycol) succinate, abbreviated as TPGS...
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| Published in | Langmuir Vol. 35; no. 31; pp. 10068 - 10078 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Chemical Society
06.08.2019
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Ultrasound contrast agents consist of stabilized microbubbles. We are developing a surfactant-stabilized microbubble platform with a shell composed of Span 60 (Sorbitan monostearate) and an emulsifying agent, water-soluble vitamin E (α-tocopheryl poly(ethylene glycol) succinate, abbreviated as TPGS), named SE61. The microbubbles act both as an imaging agent and a vehicle for delivering oxygen to hypoxic areas in tumors. For clinical use, it is important that a platform be stable under storage at room temperature. To accomplish this, a majority of biologicals are prepared as freeze-dried powders, which also eliminates the necessity of a cold chain. The interfaces among the surfactants, gas, and liquids are subject to disruption in both the freezing and drying phases. Using thermocouples to monitor temperature profiles, differential scanning calorimetry to determine the phase transitions, and acoustic properties to gauge the degree of microbubble disruption, the effects of the freezing rate and the addition of different concentrations of lyoprotectants were determined. Slower cooling rates achieved by freezing the samples in a −20 °C bath were found to be reproducible and produce contrast agents with acceptable acoustical properties. The ionic strength of the solutions and the concentration of the lyoprotectant determined the glass-transition temperature (T g′) of the frozen sample, which determines at what temperature samples can be dried without collapse. Crucially, we found that the shelf stability of surfactant-shelled oxygen microbubbles can be enhanced by increasing the lyoprotectant (glucose) concentration from 1.8 to 5.0% (w/v), which prevents the melt temperature (T m) of the TPGS phase from rising above room temperature. The increase in glucose concentration results in a lowering of T m of the emulsifying agent, preventing a phase change in the liquid-crystalline phase and allowing for more stable bubbles. We believe that preventing this phase change is necessary to producing stabilized freeze-dried microbubbles. |
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| AbstractList | Ultrasound contrast agents consist of stabilized microbubbles. We are developing a surfactant-stabilized microbubble platform with a shell composed of Span 60 (Sorbitan monostearate) and an emulsifying agent, water-soluble vitamin E (α-tocopheryl poly(ethylene glycol) succinate, abbreviated as TPGS), named SE61. The microbubbles act both as an imaging agent and a vehicle for delivering oxygen to hypoxic areas in tumors. For clinical use, it is important that a platform be stable under storage at room temperature. To accomplish this, a majority of biologicals are prepared as freeze-dried powders, which also eliminates the necessity of a cold chain. The interfaces among the surfactants, gas, and liquids are subject to disruption in both the freezing and drying phases. Using thermocouples to monitor temperature profiles, differential scanning calorimetry to determine the phase transitions, and acoustic properties to gauge the degree of microbubble disruption, the effects of the freezing rate and the addition of different concentrations of lyoprotectants were determined. Slower cooling rates achieved by freezing the samples in a −20 °C bath were found to be reproducible and produce contrast agents with acceptable acoustical properties. The ionic strength of the solutions and the concentration of the lyoprotectant determined the glass-transition temperature (T g′) of the frozen sample, which determines at what temperature samples can be dried without collapse. Crucially, we found that the shelf stability of surfactant-shelled oxygen microbubbles can be enhanced by increasing the lyoprotectant (glucose) concentration from 1.8 to 5.0% (w/v), which prevents the melt temperature (T m) of the TPGS phase from rising above room temperature. The increase in glucose concentration results in a lowering of T m of the emulsifying agent, preventing a phase change in the liquid-crystalline phase and allowing for more stable bubbles. We believe that preventing this phase change is necessary to producing stabilized freeze-dried microbubbles. Ultrasound contrast agents consist of stabilized microbubbles. We are developing a surfactant-stabilized microbubble platform with a shell composed of Span 60 (Sorbitan monostearate) and an emulsifying agent, water-soluble vitamin E ( α -tocopheryl poly(ethylene glycol) succinate, abbreviated as TPGS), named SE61. The microbubbles act both as an imaging agent and a vehicle for delivering oxygen to hypoxic areas in tumors. For clinical use, it is important that a platform be stable under storage at room temperature. To accomplish this, a majority of biologicals are prepared as freeze-dried powders, which also eliminates the necessity of a cold chain. The interfaces among the surfactants, gas, and liquids are subject to disruption in both the freezing and drying phases. Using thermocouples to monitor temperature profiles, differential scanning calorimetry to determine the phase transitions, and acoustic properties to gauge the degree of microbubble disruption, the effects of the freezing rate and the addition of different concentrations of lyoprotectants were determined. Slower cooling rates achieved by freezing the samples in a −20 °C bath were found to be reproducible and produce contrast agents with acceptable acoustical properties. The ionic strength of the solutions and the concentration of the lyoprotectant determined the glass-transition temperature ( T g ′) of the frozen sample, which determines at what temperature samples can be dried without collapse. Crucially, we found that the shelf stability of surfactant-shelled oxygen microbubbles can be enhanced by increasing the lyoprotectant (glucose) concentration from 1.8 to 5.0% (w/v), which prevents the melt temperature ( T m ) of the TPGS phase from rising above room temperature. The increase in glucose concentration results in a lowering of T m of the emulsifying agent, preventing a phase change in the liquid-crystalline phase and allowing for more stable bubbles. We believe that preventing this phase change is necessary to producing stabilized freeze-dried microbubbles. Ultrasound contrast agents consist of stabilized microbubbles. We are developing a surfactant-stabilized microbubble platform with a shell composed of Span 60 (Sorbitan monostearate) and an emulsifying agent, water-soluble vitamin E (α-tocopheryl poly(ethylene glycol) succinate, abbreviated as TPGS), named SE61. The microbubbles act both as an imaging agent and a vehicle for delivering oxygen to hypoxic areas in tumors. For clinical use, it is important that a platform be stable under storage at room temperature. To accomplish this, a majority of biologicals are prepared as freeze-dried powders, which also eliminates the necessity of a cold chain. The interfaces among the surfactants, gas, and liquids are subject to disruption in both the freezing and drying phases. Using thermocouples to monitor temperature profiles, differential scanning calorimetry to determine the phase transitions, and acoustic properties to gauge the degree of microbubble disruption, the effects of the freezing rate and the addition of different concentrations of lyoprotectants were determined. Slower cooling rates achieved by freezing the samples in a -20 °C bath were found to be reproducible and produce contrast agents with acceptable acoustical properties. The ionic strength of the solutions and the concentration of the lyoprotectant determined the glass-transition temperature (Tg') of the frozen sample, which determines at what temperature samples can be dried without collapse. Crucially, we found that the shelf stability of surfactant-shelled oxygen microbubbles can be enhanced by increasing the lyoprotectant (glucose) concentration from 1.8 to 5.0% (w/v), which prevents the melt temperature (Tm) of the TPGS phase from rising above room temperature. The increase in glucose concentration results in a lowering of Tm of the emulsifying agent, preventing a phase change in the liquid-crystalline phase and allowing for more stable bubbles. We believe that preventing this phase change is necessary to producing stabilized freeze-dried microbubbles.Ultrasound contrast agents consist of stabilized microbubbles. We are developing a surfactant-stabilized microbubble platform with a shell composed of Span 60 (Sorbitan monostearate) and an emulsifying agent, water-soluble vitamin E (α-tocopheryl poly(ethylene glycol) succinate, abbreviated as TPGS), named SE61. The microbubbles act both as an imaging agent and a vehicle for delivering oxygen to hypoxic areas in tumors. For clinical use, it is important that a platform be stable under storage at room temperature. To accomplish this, a majority of biologicals are prepared as freeze-dried powders, which also eliminates the necessity of a cold chain. The interfaces among the surfactants, gas, and liquids are subject to disruption in both the freezing and drying phases. Using thermocouples to monitor temperature profiles, differential scanning calorimetry to determine the phase transitions, and acoustic properties to gauge the degree of microbubble disruption, the effects of the freezing rate and the addition of different concentrations of lyoprotectants were determined. Slower cooling rates achieved by freezing the samples in a -20 °C bath were found to be reproducible and produce contrast agents with acceptable acoustical properties. The ionic strength of the solutions and the concentration of the lyoprotectant determined the glass-transition temperature (Tg') of the frozen sample, which determines at what temperature samples can be dried without collapse. Crucially, we found that the shelf stability of surfactant-shelled oxygen microbubbles can be enhanced by increasing the lyoprotectant (glucose) concentration from 1.8 to 5.0% (w/v), which prevents the melt temperature (Tm) of the TPGS phase from rising above room temperature. The increase in glucose concentration results in a lowering of Tm of the emulsifying agent, preventing a phase change in the liquid-crystalline phase and allowing for more stable bubbles. We believe that preventing this phase change is necessary to producing stabilized freeze-dried microbubbles. Ultrasound contrast agents consist of stabilized microbubbles. We are developing a surfactant-stabilized microbubble platform with a shell composed of Span 60 (Sorbitan monostearate) and an emulsifying agent, water-soluble vitamin E (α-tocopheryl poly(ethylene glycol) succinate, abbreviated as TPGS), named SE61. The microbubbles act both as an imaging agent and a vehicle for delivering oxygen to hypoxic areas in tumors. For clinical use, it is important that a platform be stable under storage at room temperature. To accomplish this, a majority of biologicals are prepared as freeze-dried powders, which also eliminates the necessity of a cold chain. The interfaces among the surfactants, gas, and liquids are subject to disruption in both the freezing and drying phases. Using thermocouples to monitor temperature profiles, differential scanning calorimetry to determine the phase transitions, and acoustic properties to gauge the degree of microbubble disruption, the effects of the freezing rate and the addition of different concentrations of lyoprotectants were determined. Slower cooling rates achieved by freezing the samples in a -20 °C bath were found to be reproducible and produce contrast agents with acceptable acoustical properties. The ionic strength of the solutions and the concentration of the lyoprotectant determined the glass-transition temperature ( ') of the frozen sample, which determines at what temperature samples can be dried without collapse. Crucially, we found that the shelf stability of surfactant-shelled oxygen microbubbles can be enhanced by increasing the lyoprotectant (glucose) concentration from 1.8 to 5.0% (w/v), which prevents the melt temperature ( ) of the TPGS phase from rising above room temperature. The increase in glucose concentration results in a lowering of of the emulsifying agent, preventing a phase change in the liquid-crystalline phase and allowing for more stable bubbles. We believe that preventing this phase change is necessary to producing stabilized freeze-dried microbubbles. Ultrasound contrast agents consist of stabilized microbubbles. We are developing a surfactant-stabilized microbubble platform with a shell composed of Span 60 (Sorbitan monostearate) and an emulsifying agent, water-soluble vitamin E (α-tocopheryl poly(ethylene glycol) succinate, abbreviated as TPGS), named SE61. The microbubbles act both as an imaging agent and a vehicle for delivering oxygen to hypoxic areas in tumors. For clinical use, it is important that a platform be stable under storage at room temperature. To accomplish this, a majority of biologicals are prepared as freeze-dried powders, which also eliminates the necessity of a cold chain. The interfaces among the surfactants, gas, and liquids are subject to disruption in both the freezing and drying phases. Using thermocouples to monitor temperature profiles, differential scanning calorimetry to determine the phase transitions, and acoustic properties to gauge the degree of microbubble disruption, the effects of the freezing rate and the addition of different concentrations of lyoprotectants were determined. Slower cooling rates achieved by freezing the samples in a −20 °C bath were found to be reproducible and produce contrast agents with acceptable acoustical properties. The ionic strength of the solutions and the concentration of the lyoprotectant determined the glass-transition temperature (Tg′) of the frozen sample, which determines at what temperature samples can be dried without collapse. Crucially, we found that the shelf stability of surfactant-shelled oxygen microbubbles can be enhanced by increasing the lyoprotectant (glucose) concentration from 1.8 to 5.0% (w/v), which prevents the melt temperature (Tₘ) of the TPGS phase from rising above room temperature. The increase in glucose concentration results in a lowering of Tₘ of the emulsifying agent, preventing a phase change in the liquid-crystalline phase and allowing for more stable bubbles. We believe that preventing this phase change is necessary to producing stabilized freeze-dried microbubbles. |
| Author | Vaidya, Purva Eisenbrey, John R Shraim, Rawan Oeffinger, Brian E Ayaz, Iman Wheatley, Margaret A |
| AuthorAffiliation | Department of Radiology School of Biomedical Engineering Science and Health Systems |
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| Author_xml | – sequence: 1 givenname: Brian E surname: Oeffinger fullname: Oeffinger, Brian E organization: School of Biomedical Engineering Science and Health Systems – sequence: 2 givenname: Purva surname: Vaidya fullname: Vaidya, Purva organization: School of Biomedical Engineering Science and Health Systems – sequence: 3 givenname: Iman surname: Ayaz fullname: Ayaz, Iman organization: School of Biomedical Engineering Science and Health Systems – sequence: 4 givenname: Rawan surname: Shraim fullname: Shraim, Rawan organization: School of Biomedical Engineering Science and Health Systems – sequence: 5 givenname: John R surname: Eisenbrey fullname: Eisenbrey, John R organization: Department of Radiology – sequence: 6 givenname: Margaret A orcidid: 0000-0001-6917-8972 surname: Wheatley fullname: Wheatley, Margaret A email: MAW25@Drexel.edu organization: School of Biomedical Engineering Science and Health Systems |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30827115$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_j_ultrasmedbio_2021_01_032 crossref_primary_10_1016_j_jbiosc_2021_08_010 crossref_primary_10_1038_s43246_024_00670_6 crossref_primary_10_1038_s41598_021_82602_9 crossref_primary_10_1021_acs_molpharmaceut_2c00416 crossref_primary_10_1016_j_zemedi_2023_04_007 crossref_primary_10_1039_C9SM01516G crossref_primary_10_1021_acs_langmuir_3c02773 crossref_primary_10_1016_j_colsurfb_2021_112049 crossref_primary_10_1021_acsomega_0c05518 crossref_primary_10_3390_polym14081568 crossref_primary_10_1021_acs_langmuir_9b02404 crossref_primary_10_1016_j_ijpharm_2022_122072 crossref_primary_10_3390_pharmaceutics15041302 crossref_primary_10_1016_j_colsurfa_2020_124471 |
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| SubjectTerms | acoustic properties ambient temperature cold Contrast Media - chemistry cooling differential scanning calorimetry Drug Carriers - chemistry Drug Stability emulsifiers Emulsifying Agents - chemistry Freeze Drying freezing glass transition temperature glucose Hexoses - chemistry image analysis ionic strength melting Microbubbles neoplasms oxygen Oxygen - chemistry Phase Transition polyethylene glycol powders storage temperature surfactants temperature profiles thermocouples ultrasonics vitamin E Vitamin E - chemistry water-soluble vitamins |
| Title | Preserving the Integrity of Surfactant-Stabilized Microbubble Membranes for Localized Oxygen Delivery |
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