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A Novel Thermal-driven Self-assembly Method to Prepare Albumin Nanoparticles: Formation Kinetics, Degradation Behavior and Formation Mechanism

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Abstract

Nanoparticles based on bovine serum albumin (BSA), which shares 76% homology with human serum albumin (HSA), have emerged as a promising candidate for the efficient delivery of anticancer drugs. Thermal-driven self-assembly is a novel organic solvent-free approach to produce albumin nanoparticles. In our previous study, some features of this nanoparticle such as drug loading efficiency, drug encapsulation efficiency and drug release kinetics have been evaluated. However, the formation mechanism that determines the above nanoparticle properties remains unclear. Here, we investigated the formation kinetics and mechanism using spectroscopic methods including fluorescence spectroscopy, circular dichroism (CD) and differential scanning calorimetry (DSC). We also applied chemical analysis methods that measured the content changes of albumin active groups and vanillin. To verify the covalent networks in the nanoparticles, trypsin and glutathione (GSH) were used separately to cleave the peptide bonds and disulfide bridges, and dynamic light scattering (DLS) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were used to analyze the degraded samples. BSA nanoparticles started to form at 10 min and were completely formed at 120 min. With the digestion of trypsin, more than 50% of the nanoparticles were degraded within 60 min. CD spectra showed that α-helical structure of BSA decreased from 42.3% to 39.8% and 37.7% after heating for 10 and 60 min, respectively. In the DSC thermogram, the melting peak of BSA nanoparticles was 229.14℃, which is about 12℃ higher than the physical mixture of BSA and vanillin, indicating that chemical reactions occurred during the nanoparticle formation and formed a new more stable substance. Moreover, the results of active group assay, GSH degradation and SDS-PAGE experiments also proved that disulfide bonds and peptide bonds were formed between BSA molecules, whereas Schiff bases were formed between BSA and vanillin molecules. Formation kinetics and degradation behavior are important properties to characterize albumin nanoparticles and should be paid attention to. Not only that, this study also provides an effective way to study the formation mechanism of protein-based nanodrug delivery systems.

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Funding

This work was supported by the Natural Science Foundation of Jiangsu Province (No.BK20180273), the “Qing-Lan” Project of Jiangsu Colleges, the Natural Science Research Projects of Universities in Jiangsu Province (No.18KJB360015), the National Subject Cultivation Project of Jiangsu Vocational College of Medicine (No.20204306) and the Research Startup Fund of Jiangsu Vocational College of Medicine (No.20216104).

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Author notes

  1. Fang Li and Stacy Yeh have contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Jiangsu Vocational College of Medicine, Yancheng, 224005, China

    Fang Li, Qin Shi, Hongyan Wu & Junbo Xin

  2. Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, 27157, USA

    Stacy Yeh

  3. School of Pharmaceutical Engineering, Yancheng Teachers University, Yancheng, 224007, China

    Peng Wang

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  1. Fang Li
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Contributions

Fang Li: Conceptualization, Methodology, Investigation, Writing- Original draft preparation. Stacy Yeh: Formal analysis, Writing - Review & Editing. Qin Shi: Resources, Visualization. Peng Wang: Data Curation. Hongyan Wu: Investigation. Junbo Xin: Conceptualization, Methodology.

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Li, F., Yeh, S., Shi, Q. et al. A Novel Thermal-driven Self-assembly Method to Prepare Albumin Nanoparticles: Formation Kinetics, Degradation Behavior and Formation Mechanism. AAPS PharmSciTech 23, 250 (2022). https://doi.org/10.1208/s12249-022-02407-5

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