Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties
Human serum albumin (HSA) is a multifunctional protein, known to be a natural carrier for a number of endogenous and exogenous compounds, including drugs. HSA-based drugs formulation is a clinically validated approach to improve pharmacological properties and biodistribution (such as in Abraxane). B...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Future Pharmacology |
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| Online Access: | https://www.mdpi.com/2673-9879/4/1/10 |
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| author | Tatiana Yu Kopnova Linara R. Yakupova Natalya Georgievna Belogurova Elena Vadimovna Kudryashova |
| author_facet | Tatiana Yu Kopnova Linara R. Yakupova Natalya Georgievna Belogurova Elena Vadimovna Kudryashova |
| author_sort | Tatiana Yu Kopnova |
| collection | DOAJ |
| description | Human serum albumin (HSA) is a multifunctional protein, known to be a natural carrier for a number of endogenous and exogenous compounds, including drugs. HSA-based drugs formulation is a clinically validated approach to improve pharmacological properties and biodistribution (such as in Abraxane). Based on this, one might like to modify HSA in a way that its distribution is more favorable for certain therapeutic purposes. Levofloxacin (LV), a broad-spectrum antibiotic drug, could benefit from extended systemic exposure, and stronger interactions with plasma proteins could be useful for this purpose. We engrafted monomeric or polymeric cyclodextrins (CDs) on the surface of HSA molecules to strengthen the LV adsorption (the CD−LV dissociation constant is three orders of magnitude lower than that of HSA−LV). We found that (HSA−HPolS)<sub>conj</sub>+LV exhibited the highest activity against <i>E. coli</i>, whereas (HSA−HPCD)<sub>conj</sub>+LV was the most effective against <i>B. subtilis</i>, and both HSA conjugates were more potent than LV alone or LV with HSA. Further fine-tuning of HSA could yield an improvement in biodistribution and thus a more favorable risk/benefit ratio. |
| first_indexed | 2024-04-24T18:16:23Z |
| format | Article |
| id | doaj.art-e85600ce276f4e26b939c080c689628b |
| institution | Directory Open Access Journal |
| issn | 2673-9879 |
| language | English |
| last_indexed | 2024-04-24T18:16:23Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Future Pharmacology |
| spelling | doaj.art-e85600ce276f4e26b939c080c689628b2024-03-27T13:42:21ZengMDPI AGFuture Pharmacology2673-98792024-02-014113916210.3390/futurepharmacol4010010Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological PropertiesTatiana Yu Kopnova0Linara R. Yakupova1Natalya Georgievna Belogurova2Elena Vadimovna Kudryashova3Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaChemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaChemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaChemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaHuman serum albumin (HSA) is a multifunctional protein, known to be a natural carrier for a number of endogenous and exogenous compounds, including drugs. HSA-based drugs formulation is a clinically validated approach to improve pharmacological properties and biodistribution (such as in Abraxane). Based on this, one might like to modify HSA in a way that its distribution is more favorable for certain therapeutic purposes. Levofloxacin (LV), a broad-spectrum antibiotic drug, could benefit from extended systemic exposure, and stronger interactions with plasma proteins could be useful for this purpose. We engrafted monomeric or polymeric cyclodextrins (CDs) on the surface of HSA molecules to strengthen the LV adsorption (the CD−LV dissociation constant is three orders of magnitude lower than that of HSA−LV). We found that (HSA−HPolS)<sub>conj</sub>+LV exhibited the highest activity against <i>E. coli</i>, whereas (HSA−HPCD)<sub>conj</sub>+LV was the most effective against <i>B. subtilis</i>, and both HSA conjugates were more potent than LV alone or LV with HSA. Further fine-tuning of HSA could yield an improvement in biodistribution and thus a more favorable risk/benefit ratio.https://www.mdpi.com/2673-9879/4/1/10levofloxacinhuman serum albuminhydroxypropyl-β-cyclodextrinconjugatedrug delivery systemsantibacterial activity |
| spellingShingle | Tatiana Yu Kopnova Linara R. Yakupova Natalya Georgievna Belogurova Elena Vadimovna Kudryashova Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties Future Pharmacology levofloxacin human serum albumin hydroxypropyl-β-cyclodextrin conjugate drug delivery systems antibacterial activity |
| title | Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties |
| title_full | Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties |
| title_fullStr | Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties |
| title_full_unstemmed | Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties |
| title_short | Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties |
| title_sort | human serum albumin grafted by monomeric and polymeric β cyclodextrin as drug delivery system for levofloxacin with improved pharmacological properties |
| topic | levofloxacin human serum albumin hydroxypropyl-β-cyclodextrin conjugate drug delivery systems antibacterial activity |
| url | https://www.mdpi.com/2673-9879/4/1/10 |
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