Abstract
Aminoglycosides are often subtherapeutic to intracellular infections due to their high hydrophilicity. Here we used hyaluronic acid (HA) as a carbohydrate carrier of the aminoglycoside antibiotic, amikacin (AM) to deal with intracellular bacterial infections. The hyaluronan-amikacin conjugate (HA-AM) was synthesized by ‘click’ reaction between HA-propargyl amide (HAPA) and AM-azide. This conjugate with little cytotoxicity retained antibiotic effects on planktonic bacteria and showed better intracellular bactericidal activity than the antibiotic did. In addition, this conjugate was more efficient in reducing bacteria burden in an in vivo acute infection model than amikacin did. These results suggested that hyaluronic acid conjugation could reduce the dosage of antibiotic in treatment of intracellular bacterial infection, and further helping to alleviate the emergence of drug resistance in bacteria due to a long-term, high-dosage treatment.
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