Disclosing the Potential of Fluorinated Ionic Liquids as Interferon-Alpha 2b Delivery Systems

Abstract

Interferon-alpha 2b (IFN-α 2b) is a therapeutic protein used for the treatment of cancer, viral infections, and auto-immune diseases. Its application is hindered by a low bioavailability and instability in the bloodstream, and the search for new strategies for a target delivery and stabilization of IFN-α 2b to improve its therapeutic efficacy is crucial. Fluorinated ionic liquids (FILs) are promising biomaterials that: (i) can form self-assembled structures; (ii) have complete miscibility in water; and (iii) can be designed to have reduced toxicity. The influence of IFN-α 2b in the aggregation behaviour of FILs and the interactions between them were investigated through conductivity and surface tension measurements, and using electron microscopic and spectroscopy techniques to study FILs feasibility as an interferon-alpha 2b delivery system. The results show that the presence of IFN-α 2b influences the aggregation behaviour of FILs and that strong interaction between the two compounds occurs. The protein might not be fully encapsulated by FILs. However, the FIL can be tailored in the future to carry IFN-α 2b by the formation of a conjugate, which prevents the aggregation of this protein. This work constitutes a first step toward the design and development of FIL-based IFN-α 2b delivery systems.

Simultaneous Purification of Human Interferon Alpha-2b and Serum Albumin Using Bioprivileged Fluorinated Ionic Liquid-Based Aqueous Biphasic Systems

“…The development of functionalized, bioprivileged, task-specific FILs was previously achieved through the increasing of the perfluoroalkyl sulfonate anion chain ([C F SO ] or greater) [ 37 , 67 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. These FILs have demonstrated distinct transitions associated with the formation of stable self-assembled structures, which might explain its complete miscibility in water [ 71 ].…”

“…The FILs, based on the [C F SO ] anion implemented in this study, demonstrated to be biocompatible and non-toxic in four human cell lines (Caco-2, HepG2, EA.hy926, and HaCaT) and aquatic species with different biological organization levels ( Vibrio fischeri , Daphnia magna , and Lemna minor ) [ 72 , 73 ]. The effects of these biocompatible FILs using lysozyme, BSA, human phenylalanine hydroxylase, and IFN- 2b as model proteins [ 37 , 74 , 75 , 76 , 77 ] were evaluated, proving the [C F SO ]-based FILs as promising potential biomaterials for drug delivery systems using therapeutic proteins. The formation of aqueous biphasic systems using these biocompatible FILs, based on perfluoroalkyl sulfonate anions, was first proposed by one of the authors [ 54 ] as an extractive platform, proving its potential for the efficient and selective extraction of food colorants.…”

“…In previous works [ 37 , 74 , 75 , 77 , 98 ], we developed biocompatible perfluoroalkyl sulfonate-based FILs that allow complex formation between the FIL aggregates with IFN- 2b, BSA, and Lys. Further, we developed functionalized ABSs based on these perfluoroalkyl sulfonate FILs for the selective partitions of IFN- 2b and BSA, assessed herein, and the selective partition of Lys in a previous study [ 78 ].…”

“…The efficacy and safety of therapeutic proteins are related to the folded conformation of the protein, and different manipulations in extraction or purification steps have the potential to alter the active ingredient. DSC is used in different studies to address protein folding and stability [ 99 ], as well as CD, an analytical method often used to examine structural changes that occur when a protein interacts with another molecule [ 37 , 74 , 76 , 77 , 100 ] (and references cited therein). Herein, the impact of the ABS phase on the stability and structure of IFN- 2b and BSA was assessed and compared with the behavior of the proteins in water.…”

“…Additionally, they were shown to be biocompatible and non-toxic in four human cell lines (Caco-2, HepG2, EA.hy926, and HaCaT) and aquatic species with different levels of biological organization (Vibrio fischeri, Daphnia magna, and Lemna minor) [ 72 , 73 ]. Further, the effect of these biocompatible FILs using lysozyme, BSA, human phenylalanine hydroxylase, and IFN- 2b as model proteins [ 37 , 74 , 75 , 76 , 77 ] was evaluated, showcasing these FILs as promising potential biomaterials for drug delivery systems using therapeutic proteins. Finally, the functionalization of ABS was attained through the development of biocompatible ABS based on these perfluoroalkyl sulfonate FILs for the selective partition of lysozyme as the model protein [ 78 ].…”