Abstract
Antimicrobial resistance is one of the greatest threats to global health. Although the efforts in antibiotic drug discovery continue to play a pivotal role, this solution alone probably will not be enough to ensure the required level of infection control in the future. New strategies and innovative modes of action are desperately needed to preserve the effectiveness of antimicrobials. Accordingly, antibiotic delivery based on polymeric nanoparticles is one of the possible methods that has been recently explored to improve their pharmacokinetic profile. Through optimized access of antibiotics to their sites of action, nanocarriers can unlock the full potential of the antibiotic cargoes, extend the antimicrobial spectrum, and reduce the required dose of antibiotic while preserving efficacy. Additionally, the use of an antibiotic-loaded nanocarrier is also considered a steady solution as novel molecules can be continuously developed and incorporated into the delivery platform. This review describes the present state of polymeric nanocarriers in enhancing antibiotic treatment, including improved pharmacokinetic properties and restored antibiotic efficacy against drug-resistant bacteria. Additionally, the current challenges and the future direction of this field are discussed.
Highlights
Antibiotic resistance is one of the greatest threats to human health today
By designing NPs based on polyphosphoester or phosphoester bonds, which can be readily degraded by bacterial lipases, many reported drug delivery nanosystems allowed for a precise release of antibiotics at the site of inflammation, eliminating undesirable side effects caused by premature antibiotic leakage [54,55,56,57,58,59]
The nanocarrier-based drug combination therapy has been widely applied for the treatment of biofilm infections by co-delivering antibiotics and biofilmdispersing enzymes, which are capable of degrading extracellular polymeric substances (EPS) components, such as proteins, eDNA, polysaccharides, or quorum-sensing molecules (Table 4) [136,137,138,139]
Summary
Antibiotic resistance is one of the greatest threats to human health today. efforts have been made to ensure a sustainable flow of new antibacterial drugs, especially those with novel mechanisms of action, the emergence and spread of antibiotic resistance seems inevitable. The spatiotemporal heterogeneity in the antibiotic exposure has been shown to facilitate the antibiotic resistance evolution and enable pathogenic populations to obtain a higher level of resistance than in homogeneous antibiotic concentrations [7] All these obstacles highlight the need for research to find effective antibiotic delivery platforms. A suitable dosage form of antibiotics improves therapeutic efficacy and reduces off-target effects, systemic toxicity, and the development of resistance, thereby extending the lifespan of current antibiotics. This is crucial, at least in the short term, as novel antibiotics are not likely to enter widespread clinical practice in the immediate future [8,9]. The current challenge and future direction of nanocarrier-based drug delivery systems for antimicrobial therapy are discussed
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