Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency
The inclusion of fluorine motifs in drugs and drug delivery systems is an established tool for modulating their biological potency. Fluorination can improve drug specificity or boost the vehicle’s ability to cross cellular membranes. However, the approach has yet to be applied to vaccine adjuvants....
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/10/4218 |
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| author | Harichandra D. Tagad Alexander Marin Ruixue Wang Abdul S. Yunus Thomas R. Fuerst Alexander K. Andrianov |
| author_facet | Harichandra D. Tagad Alexander Marin Ruixue Wang Abdul S. Yunus Thomas R. Fuerst Alexander K. Andrianov |
| author_sort | Harichandra D. Tagad |
| collection | DOAJ |
| description | The inclusion of fluorine motifs in drugs and drug delivery systems is an established tool for modulating their biological potency. Fluorination can improve drug specificity or boost the vehicle’s ability to cross cellular membranes. However, the approach has yet to be applied to vaccine adjuvants. Herein, the synthesis of fluorinated bioisostere of a clinical stage immunoadjuvant—poly[di(carboxylatophenoxy)phosphazene], PCPP—is reported. The structure of water-soluble fluoropolymer—PCPP-F, which contains two fluorine atoms per repeat unit—was confirmed using <sup>1</sup>H, <sup>31</sup>P and <sup>19</sup>F NMR, and its molecular mass and molecular dimensions were determined using size-exclusion chromatography and dynamic light scattering. Insertion of fluorine atoms in the polymer side group resulted in an improved solubility in acidic solutions and faster hydrolytic degradation rate, while the ability to self-assemble with an antigenic protein, lysozyme—an important feature of polyphosphazene vaccine adjuvants—was preserved. In vivo assessment of PCPP-F demonstrated its greater ability to induce antibody responses to Hepatitis C virus antigen when compared to its non-fluorinated counterpart. Taken together, the superior immunoadjuvant activity of PCPP-F, along with its improved formulation characteristics, demonstrate advantages of the fluorination approach for the development of this family of macromolecular vaccine adjuvants. |
| first_indexed | 2024-03-11T03:26:45Z |
| format | Article |
| id | doaj.art-c1bba17057a84218a9ce32a36ced909b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T03:26:45Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c1bba17057a84218a9ce32a36ced909b2023-11-18T02:41:03ZengMDPI AGMolecules1420-30492023-05-012810421810.3390/molecules28104218Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo PotencyHarichandra D. Tagad0Alexander Marin1Ruixue Wang2Abdul S. Yunus3Thomas R. Fuerst4Alexander K. Andrianov5Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAThe inclusion of fluorine motifs in drugs and drug delivery systems is an established tool for modulating their biological potency. Fluorination can improve drug specificity or boost the vehicle’s ability to cross cellular membranes. However, the approach has yet to be applied to vaccine adjuvants. Herein, the synthesis of fluorinated bioisostere of a clinical stage immunoadjuvant—poly[di(carboxylatophenoxy)phosphazene], PCPP—is reported. The structure of water-soluble fluoropolymer—PCPP-F, which contains two fluorine atoms per repeat unit—was confirmed using <sup>1</sup>H, <sup>31</sup>P and <sup>19</sup>F NMR, and its molecular mass and molecular dimensions were determined using size-exclusion chromatography and dynamic light scattering. Insertion of fluorine atoms in the polymer side group resulted in an improved solubility in acidic solutions and faster hydrolytic degradation rate, while the ability to self-assemble with an antigenic protein, lysozyme—an important feature of polyphosphazene vaccine adjuvants—was preserved. In vivo assessment of PCPP-F demonstrated its greater ability to induce antibody responses to Hepatitis C virus antigen when compared to its non-fluorinated counterpart. Taken together, the superior immunoadjuvant activity of PCPP-F, along with its improved formulation characteristics, demonstrate advantages of the fluorination approach for the development of this family of macromolecular vaccine adjuvants.https://www.mdpi.com/1420-3049/28/10/4218vaccine adjuvantspolyphosphazenesfluorine-containing pharmaceuticalsprotein-polymer interactionssupramolecular self-assemblyhepatitis C virus |
| spellingShingle | Harichandra D. Tagad Alexander Marin Ruixue Wang Abdul S. Yunus Thomas R. Fuerst Alexander K. Andrianov Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency Molecules vaccine adjuvants polyphosphazenes fluorine-containing pharmaceuticals protein-polymer interactions supramolecular self-assembly hepatitis C virus |
| title | Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency |
| title_full | Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency |
| title_fullStr | Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency |
| title_full_unstemmed | Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency |
| title_short | Fluorine-Functionalized Polyphosphazene Immunoadjuvant: Synthesis, Solution Behavior and In Vivo Potency |
| title_sort | fluorine functionalized polyphosphazene immunoadjuvant synthesis solution behavior and in vivo potency |
| topic | vaccine adjuvants polyphosphazenes fluorine-containing pharmaceuticals protein-polymer interactions supramolecular self-assembly hepatitis C virus |
| url | https://www.mdpi.com/1420-3049/28/10/4218 |
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