The effect of aminoglycosides on proximal tubular membranes of human kidneys

Breier, Joseph M.; Hendus, J; Scherberich, Jürgen E.; Mackenrodt, G.; Shah, P M; Stille, W; Schoeppe, W.

doi:10.1007/bf01646222

Cited by 1 publication

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“…Administration of high doses of antibiotics to attain the effective concentration of antibiotics required to kill pathogens might be associated with adverse effects such as alteration of the growth of harmless and useful organisms (e.g., bacteria in the intestine) [ 14 , 15 ] and/or toxic effects may be developed in some cases due to accumulation of antibiotics at off-target sites [ 14 , 15 ]. For example, prolonged administration of high doses of the aminoglycoside, tobramycin, can cause acute and chronic nephrotoxicity by decreasing glomerular filtration rate and altering excretion of electrolytes [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Activity of Azithromycin Encapsulated into PLGA NPs: A Potential Strategy to Overcome Efflux Resistance

et al. 2022

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Antimicrobial resistance represents a public health problem with a major negative impact on health and socioeconomic development, and is one of the biggest threats in the modern era. This requires the discovery of new approaches to control microbial infections. Nanomedicine could be one of the promising strategies to improve the treatment of microbial infections. Polymer nanoparticles (PNPs) were reported to overcome the efflux-resistant mechanism toward chemotherapeutic agents. However, to the best of our knowledge, no studies were performed to explore their ability to overcome the efflux-resistant mechanism in bacteria. In the current study, azithromycin (AZI), a macrolide antibiotic, was encapsulated into a biocompatible polymer, poly (lactic-co-glycolic acid) (PLGA) using the nano-precipitation method. The effect of the drug to polymer ratio, surfactant, and pH of the aqueous medium on particle size and drug loading percentage (DL%) were investigated in order to maximize the DL% and control the size of NPs to be around 100 nm. The antibacterial activity of AZI-PLGA NPs was investigated against AZI-resistant bacteria; Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis (E. faecalis), where the efflux mechanism was demonstrated to be one of the resistant mechanisms. AZI-PLGA NPs were safer than free AZI, as revealed from the cytotoxicity test, and were able to overcome the efflux-resistant mechanism, as revealed by decreasing the MIC of AZI-PLGA NPs by four times than free AZI. The MIC value reduced from 256 to 64 µg/mL and from >1000 to 256 µg/mL for MRSA and E. faecalis, respectively. Therefore, encapsulation of AZI into PNPs was shown to be a promising strategy to overcome the efflux-resistant mechanism towards AZI and improve its antibacterial effect. However, future investigations are necessary to explore the effect (if any) of particle size, surface charge, and material composition of PNPs on antibacterial activity. Moreover, it is essential to ascertain the safety profiles of these PNPs, the possibility of their large-scale manufacture, and if this concept could be extended to other antibiotics.

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