Lyophilization of Curcumin–Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability

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...

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Main Authors: Angeline Chua, The-Thien Tran, Siyu Pu, Jin-Won Park, Kunn Hadinoto
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/19/11731
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author Angeline Chua
The-Thien Tran
Siyu Pu
Jin-Won Park
Kunn Hadinoto
author_facet Angeline Chua
The-Thien Tran
Siyu Pu
Jin-Won Park
Kunn Hadinoto
author_sort Angeline Chua
collection DOAJ
description 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.
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spelling doaj.art-7a6604d1bd7c432fb6a63803ef6406a02023-11-23T20:38:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191173110.3390/ijms231911731Lyophilization of Curcumin–Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical StabilityAngeline Chua0The-Thien Tran1Siyu Pu2Jin-Won Park3Kunn Hadinoto4School of Chemistry Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637459, SingaporeSchool of Chemistry Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637459, SingaporeSchool of Chemistry Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637459, SingaporeSchool of Chemical and Biomolecular Engineering, Seoul University of Science and Technology, Seoul 01811, KoreaSchool of Chemistry Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637459, SingaporeAn 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.https://www.mdpi.com/1422-0067/23/19/11731curcumin nanoparticlesalbumin nanoparticlesamorphous drugsfreeze dryingprotein stability
spellingShingle Angeline Chua
The-Thien Tran
Siyu Pu
Jin-Won Park
Kunn Hadinoto
Lyophilization of Curcumin–Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability
International Journal of Molecular Sciences
curcumin nanoparticles
albumin nanoparticles
amorphous drugs
freeze drying
protein stability
title Lyophilization of Curcumin–Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability
title_full Lyophilization of Curcumin–Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability
title_fullStr Lyophilization of Curcumin–Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability
title_full_unstemmed Lyophilization of Curcumin–Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability
title_short Lyophilization of Curcumin–Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability
title_sort lyophilization of curcumin albumin nanoplex with sucrose as cryoprotectant aqueous reconstitution dissolution kinetic solubility and physicochemical stability
topic curcumin nanoparticles
albumin nanoparticles
amorphous drugs
freeze drying
protein stability
url https://www.mdpi.com/1422-0067/23/19/11731
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AT kunnhadinoto lyophilizationofcurcuminalbuminnanoplexwithsucroseascryoprotectantaqueousreconstitutiondissolutionkineticsolubilityandphysicochemicalstability