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.
Highlights
Pseudomonas aeruginosa is an aerobic gram negative bacterium which can survive in a variety of environments [1]
To facilitate the detection of non-chromophoric drugs in the aqueous media, we prepared a fluorescent tobramycin derivative, and here we report the results of our studies investigating the co-formulation of non-chromophoric tobramycin and AOT, enabling its encapsulation within, and release from, Poly-lactic-co-glycolic acid (PLGA) nanoparticles
The uptake efficiency of tobramycin by PLGA is governed by drug–polymer interactions
Summary
Pseudomonas aeruginosa is an aerobic gram negative bacterium which can survive in a variety of environments [1]. P. aeruginosa infections in immune competent patients tend to arise through physical trauma or surgical complications [2,3]. Many drugs have been shown to achieve greater therapeutic efficacy through loading within nanoparticulate drug delivery systems based on their potential for precise targeting and sustained release [9,10,11]. This formulation remains difficult to achieve for highly polar, water-soluble drugs. While the hydrophilicity of a drug can offer advantages including improved bioavailability and absorption [12], this can lead to poor loading within polymer-based nanoparticles if interactions between the drug and the polymer are weak [13]
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