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Pharmaceutical Research

, 35:10 | Cite as

Influence of Excipients on the Antimicrobial Activity of Tobramycin Against Pseudomonas aeruginosa Biofilms

  • Tania Bahamondez-Canas
  • Hugh D. C. Smyth
Research Paper

Abstract

Purpose

It is unknown if inactive pharmaceutical ingredients influence the activity of antibiotics they are co-formulated with. Recently it was found that materials acting as carbon nutrient sources for bacteria can promote bacterial dispersion from a biofilm and/or reverse the persister state of a subpopulation of bacteria within the biofilms. Both can make bacteria more susceptible to antibiotics. Thus, the aim was to identify potential excipients to improve antibiotic activity in Pseudomonas aeruginosa biofilms.

Methods

We screened 190 potential excipients alone, and in combination with tobramycin sulfate against P. aeruginosa (strain PAO1) grown planktonically or as biofilms. After the excipient screening stage, we investigated the effect of 10 selected excipients against a more virulent strain (luminescent strain UCBPP-PA14). Temporal changes in luminescence, as an indicator of bacterial proliferation, and surviving colony forming units (CFUs) from the treated PA14 biofilms were quantified.

Results

Forty-eight materials tested caused a reduction of PAO1 proliferation either alone or combined with tobramycin. L-alanine (p < 0.05), D-alanine (p > 0.05), and N-acetyl-D-glucosaminitol (p > 0.05) improved the activity of tobramycin measured by PA14 luminometry. Additionally, L-alanine and succinic acid significantly reduced the survival of PA14 biofilms (p < 0.05).

Conclusions

L-alanine, succinic acid, and N-acetyl-D-glucosaminitol may be useful as antibiotic adjuvants in future tobramycin anti-biofilm formulations.

KEY WORDS

Biofilms Cystic fibrosis Excipients Preformulation Pseudomonas aeruginosa 

Abbreviations

BHI

Brain heart infusion

CFU

Colony forming units

EPS

Extracellular polymeric substance

PA

Pseudomonas aeruginosa

PBS

Phosphate saline buffer

TOB

Tobramycin sulfate

XTT

2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H–tetrazolium-5-carboxanilide

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

The authors thank Dr. H.M.H.N. (Nihal) Bandara and Dr. Frederic Tewes for sharing their knowledge and experience in microbiology.

Tania Bahamondez-Canas would like to thank to CONICYT (Becas Chile) for the scholarship to pursue her Ph.D. studies.

Supplementary material

11095_2017_2301_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 17 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Molecular Pharmaceutics and Drug Delivery, College of PharmacyThe University of Texas at AustinAustinUSA
  2. 2.Center for Infectious DiseaseThe University of Texas at AustinAustinUSA

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