Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes
New carriers of phytosterols; acylglycerols containing natural myristic acid at <i>sn</i>-1 and <i>sn</i>-3 positions and stigmasterol residue linked to <i>sn</i>-2 position by carbonate and succinate linker have been designed and synthesized in three-step synthes...
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MDPI AG
2022-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/11/3406 |
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| author | Witold Gładkowski Aleksandra Włoch Hanna Pruchnik Anna Chojnacka Aleksandra Grudniewska Agnieszka Wysota Anna Dunal Daniel Rubiano Castro Magdalena Rudzińska |
| author_facet | Witold Gładkowski Aleksandra Włoch Hanna Pruchnik Anna Chojnacka Aleksandra Grudniewska Agnieszka Wysota Anna Dunal Daniel Rubiano Castro Magdalena Rudzińska |
| author_sort | Witold Gładkowski |
| collection | DOAJ |
| description | New carriers of phytosterols; acylglycerols containing natural myristic acid at <i>sn</i>-1 and <i>sn</i>-3 positions and stigmasterol residue linked to <i>sn</i>-2 position by carbonate and succinate linker have been designed and synthesized in three-step synthesis from dihydroxyacetone (DHA). The synthetic pathway involved Steglich esterification of DHA with myristic acid; reduction of carbonyl group of 1,3-dimyristoylpropanone and esterification of 1,3-dimyristoylglicerol with stigmasterol chloroformate or stigmasterol hemisuccinate. The structure of the obtained hybrids was established by the spectroscopic methods (NMR; IR; HRMS). Obtained hybrid molecules were used to form new liposomes in the mixture with model phospholipid and their effect on their physicochemical properties was determined, including the polarity, fluidity, and main phase transition of liposomes using differential scanning calorimetry and fluorimetric methods. The results confirm the significant effect of both stigmasterol-containing acylglycerols on the hydrophilic and hydrophobic region of liposome membranes. They significantly increase the order in the polar heads of the lipid bilayer and increase the rigidity in the hydrophobic region. Moreover, the presence of both acylglycerols in the membranes shifts the temperature of the main phase transition towards higher temperatures. Our results indicate stabilization of the bilayer over a wide temperature range (above and below the phase transition temperature), which in addition to the beneficial effects of phytosterols on human health makes them more attractive components of novel lipid nanocarriers compared to cholesterol. |
| first_indexed | 2024-03-10T01:05:35Z |
| format | Article |
| id | doaj.art-9296607ecd304b03bbdbb9caffd862fd |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T01:05:35Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9296607ecd304b03bbdbb9caffd862fd2023-11-23T14:28:11ZengMDPI AGMolecules1420-30492022-05-012711340610.3390/molecules27113406Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of LiposomesWitold Gładkowski0Aleksandra Włoch1Hanna Pruchnik2Anna Chojnacka3Aleksandra Grudniewska4Agnieszka Wysota5Anna Dunal6Daniel Rubiano Castro7Magdalena Rudzińska8Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Physics and Biophysics, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandFacultat de Biologia, Universitat de Barcelona, Avinguda de Diagonal 643, 08007 Barcelona, SpainFaculty of Food Science and Nutrition, Poznań University of Life Sciences, 60-637 Poznań, PolandNew carriers of phytosterols; acylglycerols containing natural myristic acid at <i>sn</i>-1 and <i>sn</i>-3 positions and stigmasterol residue linked to <i>sn</i>-2 position by carbonate and succinate linker have been designed and synthesized in three-step synthesis from dihydroxyacetone (DHA). The synthetic pathway involved Steglich esterification of DHA with myristic acid; reduction of carbonyl group of 1,3-dimyristoylpropanone and esterification of 1,3-dimyristoylglicerol with stigmasterol chloroformate or stigmasterol hemisuccinate. The structure of the obtained hybrids was established by the spectroscopic methods (NMR; IR; HRMS). Obtained hybrid molecules were used to form new liposomes in the mixture with model phospholipid and their effect on their physicochemical properties was determined, including the polarity, fluidity, and main phase transition of liposomes using differential scanning calorimetry and fluorimetric methods. The results confirm the significant effect of both stigmasterol-containing acylglycerols on the hydrophilic and hydrophobic region of liposome membranes. They significantly increase the order in the polar heads of the lipid bilayer and increase the rigidity in the hydrophobic region. Moreover, the presence of both acylglycerols in the membranes shifts the temperature of the main phase transition towards higher temperatures. Our results indicate stabilization of the bilayer over a wide temperature range (above and below the phase transition temperature), which in addition to the beneficial effects of phytosterols on human health makes them more attractive components of novel lipid nanocarriers compared to cholesterol.https://www.mdpi.com/1420-3049/27/11/3406new lipid nanocarriersliposomesacylglycerolsstigmasterolSteglich esterificationphysicochemical properties |
| spellingShingle | Witold Gładkowski Aleksandra Włoch Hanna Pruchnik Anna Chojnacka Aleksandra Grudniewska Agnieszka Wysota Anna Dunal Daniel Rubiano Castro Magdalena Rudzińska Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes Molecules new lipid nanocarriers liposomes acylglycerols stigmasterol Steglich esterification physicochemical properties |
| title | Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes |
| title_full | Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes |
| title_fullStr | Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes |
| title_full_unstemmed | Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes |
| title_short | Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery—Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes |
| title_sort | acylglycerols of myristic acid as new candidates for effective stigmasterol delivery design synthesis and the influence on physicochemical properties of liposomes |
| topic | new lipid nanocarriers liposomes acylglycerols stigmasterol Steglich esterification physicochemical properties |
| url | https://www.mdpi.com/1420-3049/27/11/3406 |
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