TY - JOUR

T1 - Investigating the influence of protein secondary structure on the dissolution behavior of β-lactoglobulin-based amorphous solid dispersions

AU - Zhuo, Xuezhi

AU - Tozzetti, Martina

AU - Arnous, Anis

AU - Leng, Donglei

AU - Foderà, Vito

AU - Löbmann, Korbinian

N1 - Publisher Copyright: © 2024 The Author(s)

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Amorphous solid dispersion

KW - Celecoxib

KW - Dissolution

KW - Protein secondary structure

KW - Solubility

KW - β-lactoglobulin

U2 - 10.1016/j.ijpharm.2024.123887

DO - 10.1016/j.ijpharm.2024.123887

M3 - Journal article

C2 - 38346599

AN - SCOPUS:85185604510

VL - 653

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 123887

ER -