Lyophilization of curcumin–albumin nanoplex with sucrose as cryoprotectant: aqueous reconstitution, dissolution, kinetic solubility, and physicochemical stability

• Main Authors: Chua, Angeline, Tran, The-Thien, Pu, Siyu, Park, Jin-Won, Hadinoto, Kunn
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Chemistry; Curcumin Nanoparticles; Albumin Nanoparticles
• Online Access: https://hdl.handle.net/10356/168551
• Institution: Nanyang Technological University

An amorphous curcumin (CUR) and bovine serum albumin (BSA) nanoparticle complex (nanoplex) was previously developed as a promising anticancer nanotherapy. The CUR-BSA nanoplex had been characterized in its aqueous suspension form. The present work developed a dry-powder form of the CUR-BSA nanoplex by lyophilization using sucrose as a cryoprotectant. The cryoprotective activity of sucrose was examined at sucrose mass fractions of 33.33, 50.00, and 66.66% by evaluating the lyophilized nanoplex's (1) aqueous reconstitution and (2) CUR dissolution and kinetic solubility. The physicochemical stabilizing effects of sucrose upon the nanoplex's 30-day exposures to 40 °C and 75% relative humidity were examined from (i) aqueous reconstitution, (ii) CUR dissolution, (iii) CUR and BSA payloads, (iv) amorphous form stability, and (v) BSA's structural integrity. The good cryoprotective activity of sucrose was evidenced by the preserved BSA's integrity and good aqueous reconstitution, resulting in a fast CUR dissolution rate and a high kinetic solubility (≈5-9× thermodynamic solubility), similar to the nanoplex suspension. While the aqueous reconstitution, CUR dissolution, and amorphous form were minimally affected by the elevated heat and humidity exposures, the treated nanoplex exhibited a lower BSA payload (≈7-26% loss) and increased protein aggregation postexposure. The adverse effects on the BSA payload and aggregation were minimized at higher sucrose mass fractions.