The effect of PAMAM dendrimers on the antibacterial activity of antibiotics with different water solubility.

Katarzyna Winnicka,Magdalena Wroblewska,Elzbieta Anna Tryniszewska,Pawel Tomasz Sacha,Piotr Wieczorek

doi:10.3390/molecules18078607

Katarzyna Winnicka, Magdalena Wroblewska + Show 3 more

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https://doi.org/10.3390/molecules18078607

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Abstract

Erythromycin (EM) and tobramycin (TOB) are well-known and widely used antibiotics, belonging to different therapeutic groups: macrolide and aminoglycoside, respectively. Moreover, they possess different solubility: EM is slightly soluble and TOB is freely soluble in water. It was previously demonstrated that PAMAM dendrimers enhanced the pharmacological activity of antifungal drugs by increasing their solubility. Therefore, it appears interesting to investigate the effect of PAMAM-NH2 and PAMAM-OH dendrimers generation 2 (G2) and generation 3 (G3) on the antibacterial activity of antibiotics with different water solubility. In this study it was shown that the aqueous solubility of EM was significantly increased by PAMAM dendrimers (PAMAM-NH2 and PAMAM-OH caused about 8- and 7- fold solubility increases, respectively). However, it was indicated that despite the increase in the solubility, there was only slight influence on the antibacterial activity of EM (2- and 4- fold decreases in the MBC values of EM in the presence of PAMAM-OH G3 and PAMAM-NH2 G2 or G3 for strains of Staphylococcus aureus were noted, respectively). It was also found that there was no influence of PAMAM on the antibacterial activity of hydrophilic TOB.

Highlights

Erythromycin is a mixture of macrolide antibiotics produced by a strain of Streptomyces erythreus, Erythromycin A [EM, (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-Omethyl-α-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[(3,4,6trideoxy-3-dimethyloamino-β-D-xylo-hexopyranosyl)oxy]oxacyclotetradecane-2,10-dione, Figure 1], which is slightly soluble in water, is the main component [1]
Among Polyamidoamine dendrimers (PAMAM) dendrimers harbouring a variety of functional groups, amino-terminated PAMAM possess the strongest antibacterial activity
It is generally assumed that protonated amino groups on PAMAM promote the disruption of anionic bacterial cell membranes through electrostatic interactions and they are necessary for the rupture of the lipids, other interactions might occur

Summary

Introduction

Erythromycin is a mixture of macrolide antibiotics produced by a strain of Streptomyces erythreus, Erythromycin A [EM, (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-Omethyl-α-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[(3,4,6trideoxy-3-dimethyloamino-β-D-xylo-hexopyranosyl)oxy]oxacyclotetradecane-2,10-dione, Figure 1], which is slightly soluble in water, is the main component [1]. Tobramycin [TOB, 4-O-(3-amino-3-deoxy-α-D-glucopyranosyl)-2-deoxy-6-O-(2,6-diamino-2,3,6trideoxy-α-D-ribohexopyranosyl)-L-streptamine, Figure 2] is an aminoglycoside antibiotic freely soluble in water [3]. TOB is effective against a wide variety of Gram-negative bacteria, especially the Pseudomonas species and some Gram-positive pathogens. It acts by inhibiting synthesis of protein in bacterial cells and is used in combination with other antibiotics in the treatment of infected post-operative wounds, diabetic foot or other soft-tissue bacterial diseases, gynecologic, ocular and respiratory infections, osteomyelitis, bacteremia and sepsis [4,5]

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