Nanotechnology-Based Antimicrobial Drug Delivery Systems: Strategies to Improve Therapeutic Efficacy

Abstract

The escalating global burden of antimicrobial resistance (AMR), coupled with a stagnant antibiotic discovery pipeline, has created an urgent need for delivery platforms that can restore or amplify the activity of existing antimicrobial agents. Conventional antimicrobial therapy is frequently compromised by poor aqueous solubility, rapid systemic clearance, nonspecific biodistribution, dose-limiting toxicity, and the physical barrier presented by bacterial biofilms, all of which contribute to therapeutic failure and the selection of resistant strains. Nanotechnology-based drug delivery systems (NDDSs) have emerged as a versatile strategy to overcome these obstacles by encapsulating, protecting, and directing antimicrobial payloads to the site of infection while minimizing off-target exposure. polymeric nanocarriers, lipid-based systems such as liposomes and solid lipid nanoparticles, and stimuli-responsive or biofilm-targeted nanoplatforms, summarizing their design principles, antimicrobial mechanisms, and reported therapeutic outcomes across seven comparative tables. The review further examines the mechanistic basis for enhanced efficacy, including improved membrane penetration, sustained and triggered release, biofilm disruption, and combination or synergistic delivery, before critically appraising the toxicological, manufacturing, and regulatory barriers that continue to limit clinical translation. Finally, emerging strategies-including biomimetic coatings, hybrid nanocomposites, artificial intelligence-assisted nanoparticle design, and nanoparticle-antimicrobial peptide conjugates-are discussed as promising avenues to improve therapeutic efficacy. Collectively, the evidence indicates that nanotechnology-enabled delivery can meaningfully potentiate antimicrobial therapy, although standardized characterization, long-term safety data, and scalable manufacturing remain necessary before widespread clinical adoption.