High-performance azithromycin delivery via chitosan-tryptophan modified polyethersulfone transdermal membranes

• An optimized membrane composition with 17% PES, 2% PVP, and 1.5% CS-W demonstrated a notable improvement in drug release. • The elucidation of the unique structural properties of the membrane that facilitates sustained and continuous drug release. • A drug release profile that fits the zero-order model and provides insights into the drug release mechanism. • Excellent biocompatibility of the optimized membranes with cell viability and minimal blood cell hemolysis. • Confirmation of the reusability of the optimized membrane, highlighting its potential for sustained drug delivery. This study investigates a novel asymmetric polyethersulfone (PES) membrane incorporated with chitosan-tryptophan (CS-W) for enhanced azithromycin delivery in vitro and ex vivo . Key fabrication parameters, including drug concentration (500 mg/L), membrane thickness (300μm), modifier percentage (1.5%), polymer percentage (17%), and pore maker content (2%), were optimized to improve membrane performance. The optimized CS-W membrane (M4) achieved a drug release of 407 mg/L, compared to 240 mg/L for the unmodified membrane (M1), using a 500 mg/L azithromycin solution. Cell viability reached ∼80%, and hemolysis was ∼4.6%, confirming biocompatibility. The water vapor transmission rate (WVTR) increased by 9.25 %, supporting enhanced moisture handling. Long-term testing confirmed membrane reusability. Also the evaluations showed acceptable antibacterial activity. The improved performance results from the membrane’s asymmetric structure: a dense top layer ensures sustained release, while a porous sub-layer acts as a drug reservoir. The drug release followed a zero-order kinetic model, making the membrane a promising candidate for sustained drug delivery applications.