Sustained Tobramycin (Antibiotic) Release from Poly(lactic- co -glycolic Acid)-Polymethyl Methacrylate (PLGA-PMMA) and PLGA−PLGA Core−Shell Electrospun Nanofiber Mats for Ophthalmic Drug Delivery

Abstract Postoperative ophthalmic therapy requires sustained local antibiotic delivery, whereas conventional eye drops suffer from rapid clearance and limited patient compliance. Here, electrospun nanofiber mats were developed for sustained tobramycin (antibiotic) release, with emphasis on the transition from monolithic poly(lactic-co-glycolic acid) (PLGA)-based fibers to poly(lactic-co-glycolic acid)-polymethyl methacrylate (PLGA-PMMA) core−shell architectures. Monolithic PLGA/polyvinyl alcohol (PVA) and PLGA fibers exhibited burst-dominated release, with rapid drug accessibility within minutes to hours despite changes in polymer composition and molecular weight. In contrast, coaxially electrospun PLGA-PMMA core−shell nanofibers remained structurally stable in phosphate-buffered saline (PBS) environment and substantially suppressed early release. The PMMA shell−PLGA core system released approximately 9% of the loaded tobramycin within the first 6 h and approximately 34% over 60 days, demonstrating sustained delivery from a stable nanofiber architecture. The measured release profiles were described using a single-stage desorption-limited model, and the extracted parameters revealed a clear transition from a burst-dominated monolithic release to a shell-regulated transport, with reduced accessible drug fraction, longer characteristic release time, lower effective diffusivity, and higher tobramycin desorption activation energy for the core−shell systems. These results demonstrate that architectural control, rather than polymer selection alone, is critical for suppressing burst release. The architectural control enables long-term ophthalmic drug delivery and the developed PLGA-PMMA core−shell nanofibers provide a promising platform for postoperative sustained antibiotic release.