Ionic liquids as biocompatible stabilizers of proteins

Abstract

Ionic liquids (ILs) have recently emerged as versatile solvents and additives in the field of biotechnology, particularly as stabilizers of proteins and enzymes. Of interest to the biotechnology industry is the formulation of stable biopharmaceuticals, therapeutic proteins, and vaccines which have revolutionized the treatment of many diseases including debilitating conditions such as cancers and auto-immune diseases. The stabilization of therapeutic proteins is typically achieved using additives that prevent unfolding and aggregation of these proteins during manufacture, transport, and long-term storage. To determine if ILs could be used in the formulation of stable therapeutic proteins, a thorough understanding of the effects of ILs on protein stability is needed, as well as understanding the toxicity of ILs on humans, and other considerations for formulation development such as viscosity and osmolality. In this review, we summarize recent developments on the stabilization of proteins and enzymes using ILs, with emphasis on identifying biocompatible ILs that may be suitable for the formulation of stable biopharmaceuticals in the future.

Aggregation selectivity of amyloid β1‐11 peptide in aqueous ionic liquid solutions

“…In addition, as in the case of Aβ 1-11 , the increase of the peak at~1720 cm −1 (ν C O ) due to the bmim + …COO − interaction in aqueous [bmim][SCN] solutions was higher than in the EAN solutions. The aggregation selectivity of PLGA in the two ILs investigated is consistent with the results observed in Aβ [1][2][3][4][5][6][7][8][9][10][11] , that is, the aggregation mechanism of Aβ 1-11 following the addition of ILs is similar to that of PLGA.…”

“…We present the Aβ 1-11 structure in water (X = 0) based on far-UV CD and FTIR spectra in Figure 1. As illustrated in Figure 1A, the far-UV CD profile of Aβ [1][2][3][4][5][6][7][8][9][10][11] in water was similar to that of typical disordered structures observed in various peptides, such as K7 peptide, [36] (AAKA) 2 , [37] and indolicidin. [38] Generally, oligopeptides (n < 10) are widely known to adopt the polyproline II [PPII; (φ, ψ) = (−60 , 150 )]…”

“…The results are consistent with the Hofmeister series. [24] As speculated previously, the addition of [bmim][SCN] to the studied two peptides (Aβ [1][2][3][4][5][6][7][8][9][10][11] or PLGA) induced the charged masked and the disruption of water structure due to the presence of the bmim + cation. In addition, the SCN − anion enhanced the disruption of the water structure.…”

“…[47,48] Far-UV CD spectrum of PLGA in water revealed a typical disordered structure (inset figure in Figure 4). Notably, FTIR spectral changes of PLGA in aqueous ILs solutions were similar to those of Aβ [1][2][3][4][5][6][7][8][9][10][11] . In both the IL solutions, the absorbance at 1645 cm −1 due to the disordered structure of PLGA decreased throughout the examined X.…”

“…Proteins in aqueous IL solutions exist in various states such as the unfolded state and show intermolecular β‐sheet aggregation and helical formation due to IL‐protein interactions . IL‐protein interactions have been studied based on experimental and theoretical techniques . Very recently, Islam et al .…”