Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion Preconcentrate
Malaria is one of the major life-threatening health problems worldwide. Artesunate is the most potent antimalarial drug to combat severe malaria. However, development of drug resistance, short plasma half-life, and poor bioavailability limit the efficacy of this drug. Here, we applied the dimerizati...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/13/5208 |
| _version_ | 1797591116022808576 |
|---|---|
| author | Rana Hore Nazmul Hasan Karsten Mäder Jörg Kressler |
| author_facet | Rana Hore Nazmul Hasan Karsten Mäder Jörg Kressler |
| author_sort | Rana Hore |
| collection | DOAJ |
| description | Malaria is one of the major life-threatening health problems worldwide. Artesunate is the most potent antimalarial drug to combat severe malaria. However, development of drug resistance, short plasma half-life, and poor bioavailability limit the efficacy of this drug. Here, we applied the dimerization concept to synthesize dimeric artesunate glycerol monocaprylate conjugate (D-AS-GC) by conjugating artesunate (AS) with glycerol monocaprylate (GC) via esterification reaction. D-AS-GC conjugate, AS, and GC were well characterized by <sup>1</sup>H NMR, attached proton test (APT) <sup>13</sup>C NMR and 2D NMR spectroscopy. D-AS-GC conjugate was further analyzed by ESI-TOF MS. Finally, a series of nanoemulsion preconcentrate (F1–F6) of D-AS-GC was prepared by mixing different ratios of oil and surfactant/cosurfactant and evaluated after dilution with an aqueous phase. The optimized formulation (F6) exhibits a clear nanoemulsion and the hydrodynamic diameter of the dispersed phase was determined by DLS and DOSY NMR spectroscopy. The morphology of the nanoemulsion droplets of F6 was investigated by AFM, which revealed the formation of tiny nanoemulsion droplets on a hydrophilic mica substrate. Moreover, using a less polar silicon wafer led to the formation of larger droplets with a spherical core shell-like structure. Overall, the rational design of the dimeric artesunate-based nanoemulsion preconcentrate could potentially be used in more efficient drug delivery systems. |
| first_indexed | 2024-03-11T01:33:01Z |
| format | Article |
| id | doaj.art-285c536bd2194c92b2b07e87c93740d6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T01:33:01Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-285c536bd2194c92b2b07e87c93740d62023-11-18T17:09:48ZengMDPI AGMolecules1420-30492023-07-012813520810.3390/molecules28135208Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion PreconcentrateRana Hore0Nazmul Hasan1Karsten Mäder2Jörg Kressler3Department of Chemistry, Martin Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, D-06099 Halle (Saale), GermanyDepartment of Chemistry, Martin Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, D-06099 Halle (Saale), GermanyInstitute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06099 Halle (Saale), GermanyDepartment of Chemistry, Martin Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, D-06099 Halle (Saale), GermanyMalaria is one of the major life-threatening health problems worldwide. Artesunate is the most potent antimalarial drug to combat severe malaria. However, development of drug resistance, short plasma half-life, and poor bioavailability limit the efficacy of this drug. Here, we applied the dimerization concept to synthesize dimeric artesunate glycerol monocaprylate conjugate (D-AS-GC) by conjugating artesunate (AS) with glycerol monocaprylate (GC) via esterification reaction. D-AS-GC conjugate, AS, and GC were well characterized by <sup>1</sup>H NMR, attached proton test (APT) <sup>13</sup>C NMR and 2D NMR spectroscopy. D-AS-GC conjugate was further analyzed by ESI-TOF MS. Finally, a series of nanoemulsion preconcentrate (F1–F6) of D-AS-GC was prepared by mixing different ratios of oil and surfactant/cosurfactant and evaluated after dilution with an aqueous phase. The optimized formulation (F6) exhibits a clear nanoemulsion and the hydrodynamic diameter of the dispersed phase was determined by DLS and DOSY NMR spectroscopy. The morphology of the nanoemulsion droplets of F6 was investigated by AFM, which revealed the formation of tiny nanoemulsion droplets on a hydrophilic mica substrate. Moreover, using a less polar silicon wafer led to the formation of larger droplets with a spherical core shell-like structure. Overall, the rational design of the dimeric artesunate-based nanoemulsion preconcentrate could potentially be used in more efficient drug delivery systems.https://www.mdpi.com/1420-3049/28/13/5208malariadimerizationartesunateglycerol monocaprylatedimeric artesunate glycerol monocaprylate conjugatenanoemulsion preconcentrate |
| spellingShingle | Rana Hore Nazmul Hasan Karsten Mäder Jörg Kressler Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion Preconcentrate Molecules malaria dimerization artesunate glycerol monocaprylate dimeric artesunate glycerol monocaprylate conjugate nanoemulsion preconcentrate |
| title | Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion Preconcentrate |
| title_full | Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion Preconcentrate |
| title_fullStr | Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion Preconcentrate |
| title_full_unstemmed | Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion Preconcentrate |
| title_short | Synthesis and Characterization of Dimeric Artesunate Glycerol Monocaprylate Conjugate and Formulation of Nanoemulsion Preconcentrate |
| title_sort | synthesis and characterization of dimeric artesunate glycerol monocaprylate conjugate and formulation of nanoemulsion preconcentrate |
| topic | malaria dimerization artesunate glycerol monocaprylate dimeric artesunate glycerol monocaprylate conjugate nanoemulsion preconcentrate |
| url | https://www.mdpi.com/1420-3049/28/13/5208 |
| work_keys_str_mv | AT ranahore synthesisandcharacterizationofdimericartesunateglycerolmonocaprylateconjugateandformulationofnanoemulsionpreconcentrate AT nazmulhasan synthesisandcharacterizationofdimericartesunateglycerolmonocaprylateconjugateandformulationofnanoemulsionpreconcentrate AT karstenmader synthesisandcharacterizationofdimericartesunateglycerolmonocaprylateconjugateandformulationofnanoemulsionpreconcentrate AT jorgkressler synthesisandcharacterizationofdimericartesunateglycerolmonocaprylateconjugateandformulationofnanoemulsionpreconcentrate |