Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties

Kopnova, T.Y.; Yakupova, L.R.; Belogurova, N.G.; Kudryashova, E.V.

Авторы: Kopnova Tatiana Yu, Yakupova Linara R., Belogurova Natalya Georgievna, Kudryashova Elena Vadimovna
Журнал: Future Pharmacology
Том: 4
Номер: 1
Год издания: 2024
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 139
Последняя страница: 162
DOI: 10.3390/futurepharmacol4010010
Аннотация: 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)conj+LV exhibited the highest activity against E. coli, whereas (HSA−HPCD)conj+LV was the most effective against B. subtilis, 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.
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Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Propertiesстатья

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