Nanoscale Organization, Thermal Properties, and Encapsulation Performance of Star-Shaped Poly(L-Lactide): Effect of Glycerol- and Diglycerol-Based Core Geometry

Single-point star-shaped poly(L-lactide) (PLLA) architectures are here synthesized using bio-sourced glycerol and diglycerol as polyfunctional initiators, to investigate the influence of polymer topology and core geometry on nanoscale organization, thermal behavior, and encapsulation of hydrophobic probes. NMR spectroscopy confirmed the branched structure while SAXS revealed architecture-dependent chain conformations in solution, with a transition from single-chain behavior to lamellar aggregation as branching and molar mass increased. Star-shaped PLLA generally showed amorphous behavior and lower thermal stability than linear PLLA. However, in the diglycerol series, increasing arm length induced semicrystalline behavior, attributed to steric constraints at the core that promote asymmetric arm growth and favor extended chains in spatially separated arms. Nanoprecipitation in water yielded nanoaggregates (ca. 200 nm in size) displaying colloidal stability up to 1 month. Encapsulation studies using usnic acid as a hydrophobic probe highlighted architecture-driven effects on amount and physical state of encapsulated compound. Diglycerol core promoted amorphous guest stabilization, suggesting that encapsulation is dictated by core-controlled arm growth and packing. Cytotoxicity assays in MDA-MB-231 triple-negative breast cancer cells showed that UA encapsulation in diglycerol-based star-shaped PLLA reduces hepatotoxicity and integrin β1 expression, supporting the system’s ability to control interfacial interactions at the bio–nano interface.