Immobilization and Intracellular Delivery of Structurally Nanoengineered Antimicrobial Peptide Polymers Using Polyphenol‐Based Capsules

Structurally nanoengineered antimicrobial peptide polymers (SNAPPs) are an emerging class of antimicrobials against multidrug-resistant bacteria. Their encapsulation in particle carriers can improve their therapeutic efficacy by preventing degradation, reducing clearance, and enhancing intracellular delivery dosage to bacteria-infected host cells. Herein, two template-mediated strategies reported for immobilizing SNAPPs microcapsules through 1) complexation with tannic acid (TA) onto porous CaCO3 templates subsequent removal the (SNAPP–TA capsules) 2) adsorption within a metal–phenolic (FeIII–TA) coating template (SNAPP–FeIII–TA capsules). The loading amounts 0.8 4.4 pg per SNAPP–TA SNAPP–FeIII–TA capsule, respectively. At pH 7.4, there is sustained release SNAPPs, which retain high activity minimum inhibitory concentration values ≈30 µg mL−1 Escherichia coli. Both capsule systems internalized alveolar macrophages vitro, negligible cytotoxicity amenable nebulization, remaining stable nebulized droplets. This study demonstrates potential engineered polyphenol-based capsules drug immobilization delivery, have prospective application pulmonary respiratory bacterial infections (e.g., pneumonia, tuberculosis).