Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles
Abstract Polymeric micro‐ and nanoparticles are useful vehicles for delivering cytokines to diseased tissues such as solid tumors. Double emulsion solvent evaporation is one of the most common techniques to formulate cytokines into vehicles made from hydrophobic polymers; however, the liquid–liquid...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Bioengineering & Translational Medicine |
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| Online Access: | https://doi.org/10.1002/btm2.10722 |
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| author | Emily R. Rhodes Nicole B. Day Emma C. Aldrich C. Wyatt Shields IV Kayla G. Sprenger |
| author_facet | Emily R. Rhodes Nicole B. Day Emma C. Aldrich C. Wyatt Shields IV Kayla G. Sprenger |
| author_sort | Emily R. Rhodes |
| collection | DOAJ |
| description | Abstract Polymeric micro‐ and nanoparticles are useful vehicles for delivering cytokines to diseased tissues such as solid tumors. Double emulsion solvent evaporation is one of the most common techniques to formulate cytokines into vehicles made from hydrophobic polymers; however, the liquid–liquid interfaces formed during emulsification can greatly affect the stability and therapeutic performance of encapsulated cytokines. To develop more effective cytokine‐delivery systems, a clear molecular understanding of the interactions between relevant proteins and solvents used in the preparation of such particles is needed. We utilized an integrated computational and experimental approach for studying the governing mechanisms by which interleukin‐12 (IL‐12), a clinically relevant cytokine, is protected from denaturation by albumin, a common stabilizing protein, at an organic‐aqueous solvent interface formed during double emulsification. We investigated protein–protein interactions between human (h)IL‐12 and albumin and simulated these components in pure water, dichloromethane (DCM), and along a water/DCM interface to replicate the solvent regimes formed during double emulsification. We observed that (i) hIL‐12 experiences increased structural deviations near the water/DCM interface, and (ii) hIL‐12 structural deviations are reduced in the presence of albumin. Experimentally, we found that hIL‐12 bioactivity is retained when released from particles in which albumin is added to the aqueous phase in molar excess to hIL‐12 and sufficient time is allowed for albumin‐hIL‐12 binding. Findings from this work have implications in establishing design principles to enhance the stability of cytokines and other unstable proteins in particles formed by double emulsification for improved stability and therapeutic efficacy. |
| format | Article |
| id | doaj-art-f3fd68ad00c54ac88a654381be4370c5 |
| institution | Kabale University |
| issn | 2380-6761 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Bioengineering & Translational Medicine |
| spelling | doaj-art-f3fd68ad00c54ac88a654381be4370c52025-01-09T06:19:46ZengWileyBioengineering & Translational Medicine2380-67612025-01-01101n/an/a10.1002/btm2.10722Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticlesEmily R. Rhodes0Nicole B. Day1Emma C. Aldrich2C. Wyatt Shields IV3Kayla G. Sprenger4Department of Chemical and Biological Engineering University of Colorado Boulder Boulder Colorado USADepartment of Chemical and Biological Engineering University of Colorado Boulder Boulder Colorado USADepartment of Chemical and Biological Engineering University of Colorado Boulder Boulder Colorado USADepartment of Chemical and Biological Engineering University of Colorado Boulder Boulder Colorado USADepartment of Chemical and Biological Engineering University of Colorado Boulder Boulder Colorado USAAbstract Polymeric micro‐ and nanoparticles are useful vehicles for delivering cytokines to diseased tissues such as solid tumors. Double emulsion solvent evaporation is one of the most common techniques to formulate cytokines into vehicles made from hydrophobic polymers; however, the liquid–liquid interfaces formed during emulsification can greatly affect the stability and therapeutic performance of encapsulated cytokines. To develop more effective cytokine‐delivery systems, a clear molecular understanding of the interactions between relevant proteins and solvents used in the preparation of such particles is needed. We utilized an integrated computational and experimental approach for studying the governing mechanisms by which interleukin‐12 (IL‐12), a clinically relevant cytokine, is protected from denaturation by albumin, a common stabilizing protein, at an organic‐aqueous solvent interface formed during double emulsification. We investigated protein–protein interactions between human (h)IL‐12 and albumin and simulated these components in pure water, dichloromethane (DCM), and along a water/DCM interface to replicate the solvent regimes formed during double emulsification. We observed that (i) hIL‐12 experiences increased structural deviations near the water/DCM interface, and (ii) hIL‐12 structural deviations are reduced in the presence of albumin. Experimentally, we found that hIL‐12 bioactivity is retained when released from particles in which albumin is added to the aqueous phase in molar excess to hIL‐12 and sufficient time is allowed for albumin‐hIL‐12 binding. Findings from this work have implications in establishing design principles to enhance the stability of cytokines and other unstable proteins in particles formed by double emulsification for improved stability and therapeutic efficacy.https://doi.org/10.1002/btm2.10722cancercytokinesinterfacial behaviormolecular dynamicsnanoparticles |
| spellingShingle | Emily R. Rhodes Nicole B. Day Emma C. Aldrich C. Wyatt Shields IV Kayla G. Sprenger Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles Bioengineering & Translational Medicine cancer cytokines interfacial behavior molecular dynamics nanoparticles |
| title | Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles |
| title_full | Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles |
| title_fullStr | Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles |
| title_full_unstemmed | Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles |
| title_short | Elucidating the role of carrier proteins in cytokine stabilization within double emulsion‐based polymeric nanoparticles |
| title_sort | elucidating the role of carrier proteins in cytokine stabilization within double emulsion based polymeric nanoparticles |
| topic | cancer cytokines interfacial behavior molecular dynamics nanoparticles |
| url | https://doi.org/10.1002/btm2.10722 |
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