Structural tuning of galactomannan-poly(ε-caprolactone) nanocapsule hybrid hydrogels mediated by 1,2,3,4-butanetetracarboxylic acid.

Abstract

Hybrid hydrogel-nanocapsule systems are promising platforms for topical drug delivery; however, the impact of polymer structural modulation on nanocapsule organization and multiscale structure-property relationships remains insufficiently understood. Herein, galactomannan-poly(ε-caprolactone) (PCL) hybrid hydrogels containing α-bisabolol-loaded nanocapsules were prepared with different BTCA concentrations to investigate the effect of polymer chain modulation on nanocapsule organization and physicochemical properties. The resulting systems were characterized by a multiscale approach combining photon correlation spectroscopy (PCS), high-performance size exclusion chromatography (HPSEC), Fourier transform infrared spectroscopy (FTIR), cryogenic transmission electron microscopy (cryo-TEM), small- and wide-angle X-ray scattering (SAXS/WAXS), differential scanning calorimetry (DSC), and rheological analysis. α-Bisabolol-loaded poly(ε-caprolactone) nanocapsules (BNC) exhibited a hydrodynamic radius of 98 ± 1 nm. HPSEC demonstrated a concentration-dependent reduction in the weight-average molar mass of galactomannan from ~1.5 ∙ 106 g/mol, confirming chain modification, consistent with FTIR analysis. WAXS and DSC confirmed preservation of the semicrystalline PCL lamellar structure under hydrated conditions, whereas rheological analyses revealed reduced chain entanglement while maintaining shear-thinning behavior. These findings establish direct structure-property relationships, demonstrating the potential of BTCA-mediated galactomannan modulation to control nanocapsule organization and engineer hybrid hydrogels for topical drug delivery.