Hierarchical PLGA/PEG Barrier Engineering of Alginate Hydrogels: Scale-Dependent Burst-Release Control in Beads and...

Alginate hydrogels offer mild ionic gelation and tunable porosity for drug delivery, yet their hydrophilic, macroporous networks suffer from rapid initial burst release of water-soluble payloads. Here we introduce a hierarchical barrier-engineering strategy in which poly(D,L-lactide-co-glycolide)/poly(ethylene glycol) (PLGA/PEG) blend coatings are applied via dip-coating to Ca²⁺-cross-linked alginate beads (~1 mm) and microgels (~100 µm). For beads, three-cycle PLGA/PEG multilayer coating suppressed the initial swelling rate (dQ/dt) by ~50% and reduced 1 h burst release from >85% to ~60%, functioning as an "early-burst buffer" rather than a long-term depot. For microgels, a single PLGA/PEG layer partially attenuated burst release; however, an additional PLGA outer shell (double-barrier architecture) shifted the release-governing mechanism from swelling-dominated to diffusion-barrier-dominated control, limiting 10 min release to <10%. Core-shell formation was verified by confocal laser scanning microscopy (CLSM), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM/EDS), Fourier-transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS); thermogravimetric analysis (TGA) showed ~73-79% coating retention after 9 days in phosphate-buffered saline (PBS, 37 °C). A vacuum re-loading process further improved encapsulation efficiency (>50% for beads, >20% for microgels) without compromising gel integrity. In beads, burst control was governed by swelling suppression; in microgels, the additional PLGA shell shifted control to diffusion-barrier-dominated release, demonstrating that barrier architecture must be adapted to particle scale.