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

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.