A new bioavailability enhancement strategy of curcumin via self-assembly nano-complexation of curcumin and bovine serum albumin

- CUR-BSA nanoplex formation favors low pH and MBSA/CUR below unity.
- CUR-BSA nanoplex characteristics are insensitive to pH and MBSA/CUR.
- CUR-BSA nanoplex has higher colloidal stability, smaller size than CUR-CHI nanoplex.
- CUR-BSA nanoplex dissolves faster with longer supersaturation than CUR-CHI nanoplex.
- CUR release from nanoplex is modulated after heat treatment at high BSA content.

Amorphous drug nanoparticles have recently emerged as a superior bioavailability enhancement strategy for poorly soluble drugs in comparison to the conventional microscale amorphous solid dispersions. In particular, amorphous drug nanoparticle complex (or nanoplex) represents an attractive bioavailability enhancement strategy of curcumin (CUR) - a medicinal herb known for its wide-ranging therapeutic activities - attributed to the high payload, cost-effective preparation, and supersaturation generation of the nanoplex. To address the poor colloidal stability of conventional nanoplex formulations, we herein developed a new class of CUR nanoplex by complexation of CUR with bovine serum albumin (BSA). The effects of two key variables in drug-protein complexation, i.e. pH and mixing ratio (MBSA/CUR), on the physical characteristics and preparation efficiency were investigated. While the CUR-BSA nanoplex preparation was found to favor acidic pH and MBSA/CUR below unity, the nanoplex's physical characteristics were minimally affected by pH and MBSA/CUR. At the optimal condition, CUR-BSA nanoplex with size ≈ 90 nm, zeta potential ≈ 27 mV, and payload ≈ 70% were produced at nearly 100% CUR utilization rate and ≈ 80% yield. The nanoplex produced a prolonged supersaturation level at ≈ 9 × of the saturation solubility for 4 h. The dissolution rate could be modulated by thermal treatment of the nanoplex post its preparation. The long-term amorphous state stability, storage colloidal stability, and preserved bioactivity of the nanoplex were successfully established. Lastly, the CUR-BSA nanoplex was found to be superior to the conventional nanoplex in its size, supersaturation generation, colloidal stability, and yield.

A supersaturating nanoscale delivery system of curcumin (CUR) prepared by complexation with bovine serum albumin (BSA).126