Investigating the influence of protein secondary structure on the dissolution behavior of β-lactoglobulin-based amorphous solid dispersions

Xuezhi Zhuo, Martina Tozzetti, Anis Arnous, Donglei Leng, Vito Foderà, Korbinian Löbmann*

*Corresponding author for this work

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Abstract

Proteins acting as carriers in amorphous solid dispersions (ASDs) demonstrate a notable sensitivity to the spray drying process, potentially leading to changes in their conformation. The main aim of this study was to investigate the dissolution performance of ASDs based on proteins with different content of secondary structures, specifically β-sheet and α-helix structures. We prepared β-sheet-rich and α-helix-rich β-lactoglobulin (BLG), along with corresponding ASDs containing 10 wt% and 30 wt% drug loadings, through spray drying using celecoxib as the model drug. Circular dichroism and Fourier Transform Infrared Spectroscopy results revealed that even though changes in secondary structure were obtained in the spray-dried powders, the BLGs exhibited reversibility upon re-dissolving in phosphate buffer with varying pH levels. Both β-sheet-rich BLG and α-helix-rich BLG exhibited enhanced dissolution rates and higher solubility in the media with pH values far from the isoelectric point (pI) of BLG (pH 2, 7, 8, and 9) compared to the pH closer to the pI (pH 3, 4, 5, and 6). Notably, the release rate and solubility of the drug and BLG from both types of BLG-based ASDs at 10 wt% drug loading were largely dependent on the solubility of pure SD-BLGs. α-helix-rich BLG-ASDs consistently exhibited equivalent or superior performance to β-sheet-rich BLG-ASDs in terms of drug release rate and solubility, regardless of drug loading. Moreover, both types of BLG-based ASDs at 10 wt% drug loading exhibited faster release rates and higher solubility, for both the drug and BLG, compared to the ASDs at 30 wt% drug loading in pHs 2, 7, and 9 media.

Original languageEnglish
Article number123887
JournalInternational Journal of Pharmaceutics
Volume653
Number of pages8
ISSN0378-5173
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Keywords

  • Amorphous solid dispersion
  • Celecoxib
  • Dissolution
  • Protein secondary structure
  • Solubility
  • β-lactoglobulin

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