The global escalation of antimicrobial resistance (AMR) poses a critical threat to modern medicine, rendering conventional antibiotics increasingly ineffective and severely limiting clinical options against multi-drug-resistant (MDR) bacterial pathogens. To overcome these pharmacological limitations, innovative drug delivery strategies and structural modulation platforms are urgently needed. Macrocyclic host architectures—including cyclodextrins, calixarenes, cucurbit[n]urils, and pillar[n]arenes—have emerged as highly versatile supramolecular platforms capable of revolutionizing antimicrobial therapy. Their unique cavity structures, customizable functionalization, and controllable host–guest complexation dynamics enable distinct targeted delivery strategies, improved drug solubility, enhanced bioactivity, and reduced systemic toxicity.

This Special Issue aims to highlight state-of-the-art research at the intersection of supramolecular chemistry, medicinal chemistry, and microbiology, specifically focusing on macrocycle-assisted antibiotic delivery and resistance modulation. Beyond serving as novel nanocarriers, functionalized macrocycles can directly perturb bacterial membrane integrity, disrupt protective biofilms, inhibit efflux pump activity, and encapsulate essential co-factors, thereby re-sensitizing resistant strains to conventional antimicrobial agents. The objective of this Special Issue is to compile cutting-edge original research articles, short communications, and comprehensive reviews that elucidate host–guest binding mechanisms, structural design principles, bio-interface interactions, and the therapeutic efficacy of macrocyclic systems in vitro and in vivo.

By bridging fundamental supramolecular complexation with translational therapeutic applications, this Special Issue seeks to foster interdisciplinary collaboration and accelerate the development of next-generation macrocycle-based antimicrobial countermeasures to combat the growing burden of drug resistance.

Original research articles, review articles and case studies.

Through this special issue on "Macrocyclic Systems in Antibiotic Delivery and Resistance Modulation: Complexation, Mechanisms, and Therapeutic Potential," we aim to consolidate groundbreaking research and foster key conceptual advancements in supramolecular antimicrobial therapies, offering a comprehensive framework for designing host–guest systems that overcome drug resistance and optimize antibiotic delivery. We welcome researchers from various disciplines—including medicinal chemistry, organic synthesis, supramolecular chemistry, microbiology, biophysics, and pharmaceutical sciences—to provide interdisciplinary perspectives on the design, complexation mechanisms, biofilm disruption, efflux pump modulation, and translational therapeutic potential of macrocyclic carriers. Your contributions will play a crucial role in advancing knowledge in this field and driving next-generation countermeasures against multi-drug-resistant pathogens.