This study presents the development of a novel drug delivery system designed for improving the release profile and sustained delivery of azithromycin (AZI), particularly aimed at applications requiring localized infection control and improved tissue compatibility. The system employs an asymmetric polyethersulfone (PES) membrane modified with KIT-6 mesoporous material, offering improved drug release performance and biocompatibility over conventional delivery platforms. Membrane optimization was achieved by systematically varying parameters such as thickness (150-600 µm), drug concentration (500-1500 mg/L), polymer content (13-21 % PES), pore maker percentage (0-4 % polyvinylpyrrolidone), and KIT-6 modifier percentage (0.5-2 %). Characterization included scanning electron microscopy, water contact angle measurements, porosity, tensile strength evaluation, and comprehensive bioactivity testing (cytotoxicity, antimicrobial efficacy, blood compatibility, and a novel tissue integrity assay). The optimized formulation (17 % PES, 2 % PVP, 1 % KIT-6) achieved a controlled and sustained release profile with improved drug availability (464 mg/L) compared to unmodified membranes (252 mg/L), with a sustained release profile governed by the Higuchi model. Additionally, the membrane demonstrated superior biocompatibility (-90 % cell viability, low hemolysis at 1.2 %) and preserved tissue integrity better than unmodified counterparts, as evidenced by in vitro and ex vivo studies. Notably, the system showed robust reusability over prolonged use, indicating its potential as an effective, sustainable, and biocompatible solution for localized AZI delivery. These advantages position this system as a promising alternative for medical applications requiring precise drug release and minimal tissue disruption.