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. 2019 Jun 13;10(2):26.
doi: 10.3390/jfb10020026.

Formulation of Antimicrobial Tobramycin Loaded PLGA Nanoparticles via Complexation with AOT

Marcus Hill  1 , Richard N Cunningham  2 , Rania M Hathout  3 , Christopher Johnston  4 , John G Hardy  5   6 , Marie E Migaud  7   8
Affiliations

Formulation of Antimicrobial Tobramycin Loaded PLGA Nanoparticles via Complexation with AOT

Marcus Hill et al. J Funct Biomater. .

Abstract

Tobramycin is a potent antimicrobial aminoglycoside and its effective delivery by encapsulation within nanoparticle carriers could increase its activity against infections through a combination of sustained release and enhanced uptake. Effective antimicrobial therapy against a clinically relevant model bacteria (Pseudomonas aeruginosa) requires sufficient levels of therapeutic drug to maintain a drug concentration above the microbial inhibitory concentration (MIC) of the bacteria. Previous studies have shown that loading of aminoglycoside drugs in poly(lactic-co-glycolic) acid (PLGA)-based delivery systems is generally poor due to weak interactions between the drug and the polymer. The formation of complexes of tobramycin with dioctylsulfosuccinate (AOT) allows the effective loading of the drug in PLGA-nanoparticles and such nanoparticles can effectively deliver the antimicrobial aminoglycoside with retention of tobramycin antibacterial function.

Keywords: antimicrobial; biomedical applications; colloids; drug delivery systems; nanoparticles.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Chemical structures investigated in this report. (A) Tobramycin; (B) Fluorescent tobramycin derivative; (C) dioctylsulfosuccinate (AOT); (D) PLGA 503 ester terminated; (E) PLGA 502H acid terminated.
Scheme 1
Scheme 1
Synthesis of a fluorescent tobramycin derivative.
Figure 2
Figure 2
Organic extraction of the fluorescent derivative of tobramycin in the presence (left) and absence (right) of AOT: top layer water, bottom layer dichloromethane.
Figure 3
Figure 3
Effect of pH on the extraction of tobramycin into dichloromethane by AOT.
Figure 4
Figure 4
Release profile of PLGA RG502H nanoparticles entrapped with tobramycin loaded AOT reverse micelles at 37 °C in PBS.
Figure 5
Figure 5
MIC analysis. (A) Unloaded nanoparticle control; (B) Free tobramycin; (C) Tobramycin loaded nanoparticles.
See this image and copyright information in PMC

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