Azithromycin-loaded linolenic acid-modified methoxy poly(ethylene glycol) micelles for bacterial infection treatment

Wen, Yurong; Song, Zhen; Xu, Hongmei; Feng, Sijia; Zhu, Li; Teng, Fangfang; Feng, Runliang

doi:10.1007/s13346-021-00953-2

Cited by 4 publications

(1 citation statement)

References 42 publications

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“…Unfortunately, about half of the chemical compounds identified as potential new medicines are poorly soluble in water 2,3 . Currently, many efforts and techniques focus on enhancing the water-solubility of lead compounds, which illustrates this property's importance for pharmacological tools [1][2][3][4][5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility

Magallón

Reeves

et al. 2021

Preprint

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Resistance to amikacin in Gram-negatives is usually mediated by the 6'-N-acetyltransferase type Ib [AAC(6')-Ib], which catalyzes the transfer of an acetyl group from acetyl CoA to the 6' position of the antibiotic molecule. A path to continue the effective use of amikacin against resistant infections is to combine it with inhibitors of the inactivating reaction. We have recently observed that addition of Zn2+ to in-vitro enzymatic reactions, obliterates acetylation of the acceptor antibiotic. Furthermore, when added to amikacin-containing culture medium in complex to ionophores such as pyrithione (ZnPT), it prevents the growth of resistant strains. An undesired property of ZnPT is its poor water-solubility, a problem that currently affects a large percentage of newly designed drugs. Water-solubility helps drugs to dissolve in body fluids and be transported to the target location. We tested a pyrithione derivative described previously (Magda et al. Cancer Res. 2008, 68:5318-5325) that contains the amphoteric group di(ethyleneglycol)-methyl ether at position 5 (compound 5002), a modification that enhances the solubility. Compound 5002 in complex with zinc (Zn5002) was tested to assess growth inhibition of amikacin-resistant Acinetobacter baumannii and Klebsiella pneumoniae strains in the presence of the antibiotic. Zn5002 complexes in combination with amikacin at different concentrations completely inhibited growth of the tested strains. However, the concentrations needed to achieve growth inhibition were higher than those required to achieve the same results using ZnPT. Time-kill assays showed that the effect of the combination amikacin/Zn5002 was bactericidal. These results indicate that derivatives of pyrithione with enhanced water-solubility, a property that would make them drugs with better bioavailability and absorption, are a viable option for designing inhibitors of the resistance to amikacin mediated by AAC(6')-Ib, an enzyme commonly found in the clinics.

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Section: Introductionmentioning

confidence: 99%

Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility

Magallón

Reeves

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

Research progress of nanoparticle targeting delivery systems in bacterial infections

Jin

Cai

et al. 2023

Colloids and Surfaces B: Biointerfaces

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Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility

Magallón

Reeves

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Resistance to amikacin in Gram-negatives is usually mediated by the 6'-N-acetyltransferase type Ib [AAC(6')-Ib], which catalyzes the transfer of an acetyl group from acetyl CoA to the 6' position of the antibiotic molecule. A path to continue the effective use of amikacin against resistant infections is to combine it with inhibitors of the inactivating reaction. We have recently observed that addition of Zn2+ to in-vitro enzymatic reactions, obliterates acetylation of the acceptor antibiotic. Furthermore, when added to amikacin-containing culture medium in complex to ionophores such as pyrithione (ZnPT), it prevents the growth of resistant strains. An undesired property of ZnPT is its poor water-solubility, a problem that currently affects a large percentage of newly designed drugs. Water-solubility helps drugs to dissolve in body fluids and be transported to the target location. We tested a pyrithione derivative described previously (Magda et al. Cancer Res 68:5318–5325, 2008) that contains the amphoteric group di(ethyleneglycol)-methyl ether at position 5 (compound 5002), a modification that enhances the solubility. Compound 5002 in complex with zinc (Zn5002) was tested to assess growth inhibition of amikacin-resistant Acinetobacter baumannii and Klebsiella pneumoniae strains in the presence of the antibiotic. Zn5002 complexes in combination with amikacin at different concentrations completely inhibited growth of the tested strains. However, the concentrations needed to achieve growth inhibition were higher than those required to achieve the same results using ZnPT. Time-kill assays showed that the effect of the combination amikacin/Zn5002 was bactericidal. These results indicate that derivatives of pyrithione with enhanced water-solubility, a property that would make them drugs with better bioavailability and absorption, are a viable option for designing inhibitors of the resistance to amikacin mediated by AAC(6')-Ib, an enzyme commonly found in the clinics.

show abstract

Azithromycin-loaded linolenic acid-modified methoxy poly(ethylene glycol) micelles for bacterial infection treatment

Cited by 4 publications

References 42 publications

Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility

Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility

Research progress of nanoparticle targeting delivery systems in bacterial infections

Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility

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