Curcumin-loaded beta-glucan nanoparticles: preparation, physicochemical properties, and molecular modeling

This study introduces the application of wet milling, a well-established top-down technique, as a novel approach for preparing beta-glucan nanoparticles (BG-NPs) as carriers for poorly soluble drugs, using curcumin (CC) as a model compound. This presents one of the first studies illustrating wet milling as a feasible way to produce BG-NPs with enhanced drug delivery capabilities, potentially improving the bioavailability of CC in particular and other poorly soluble drugs in general.

A two-step process was employed: first, optimizing beta-glucan (BG) nanocarrier preparation, followed by CC incorporation. Separating factor (NaOH) and hydrolyzing factor (CH₃COOH) were used to facilitate the size reduction of BG's robust triple-helix structure.

Under optimized conditions, BG-NPs with an average size of 408.8 ± 13.1 nm were produced. Curcumin-loaded BG-NPs (CC/BG-NPs) at the optimal drug-to-carrier ratio of 0.4:1 (w/w) achieved a particle size of approximately 300 nm with 98% loading efficiency and 84.3% drug release within 120 min, which is approximately a 4-fold increase compared to raw CC (18.4%). Solid-state analysis, FTIR spectroscopy, molecular docking, and molecular dynamics simulation confirmed the formation of hydrogen bonds between CC's carbonyl and methoxy groups with BG's hydroxyl groups, along with stabilizing hydrophobic interactions.

The optimized formulation produced uniform nanoparticles with sizes suitable for efficient cellular uptake and drug delivery. Using CC as a model drug, we demonstrated enhanced dissolution through strong intermolecular interactions between the drug and carrier.