Maintaining supersaturation generation and protein integrity of amorphous curcumin-albumin nanoplex during storage by freeze drying with trehalose

Amorphous curcumin-albumin nanoplex (size ≈ 100 nm, 55 wt% curcumin content) is a highly promising nanoscale delivery system of curcumin attributed to its high curcumin's payload and kinetic solubility. Its storage stability, however, has not been established. Previously, freeze-dried nanoplex with sucrose as stabilizer was found to lose its curcumin solubility enhancement capability after storage. The present work investigated trehalose as the freeze-dried nanoplex's stabilizer during one-month accelerated storage at 40 °C and 75% relative humidity. The investigation was performed at trehalose mass fractions between 0 and 66.66%. The storage stability was evaluated in terms of the (1) curcumin and albumin payloads, (2) albumin's structural integrity, (3) nanoplex's aggregation tendency, (4) amorphous curcumin's devitrification tendency, and (5) curcumin's dissolution profile and supersaturation generation. The results showed that amorphous curcumin in the freeze-dried nanoplex was minimally affected by storage and its fast dissolution from the nanoplex was preserved after storage. On the other hand, trehalose inclusion at > 50 wt% was needed to minimize albumin aggregation and to prevent nanoplex aggregation as evidenced by poor aqueous reconstitution after storage. At trehalose mass fraction >50%, curcumin supersaturation generation was preserved after storage owed to albumin's crystallization-inhibiting activity.