Abstract

AbstractHealthcare‐associated infections affect every year more than four million people due to the increasing resistance of bacteria to traditional antibiotics. In turn, the systematic use of quaternary ammonium salts as antiseptics is hampered by their inherent toxicity and high hydrophilicity that leads to their rapid elimination from the body. Therefore, a carefully controlled release of these antiseptics is pivotal to achieve prolonged therapeutic efficacy reducing the side effects. In this work, high encapsulation efficiencies and good control over the release of octenidine hydrochloride from poly(lactic acid) (PLA)‐based nanoparticles (NPs) is achieved by introducing functional carboxylate groups in the polymer. The influence of the polymer structure and functionalization over the drug release is systematically investigated. Star‐like and brush‐like polymers with tunable number of ionizable chain end‐groups are synthesized via combination of ring‐opening polymerization and reversible addition−fragmentation chain transfer polymerization. These polymers are formulated in NPs and loaded with octenidine through emulsion/solvent evaporation. Brush‐like polymers demonstrate to be a versatile tool for the modulation of the initial burst and long term release of the antiseptic through the tuning of the electrostatic interactions between the negative groups on the polymer, whose number can be precisely controlled, and the positively charged drug.

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