The potential of ionic liquids in biopharmaceutical engineering

doi:10.1016/j.cjche.2020.11.015

Abstract

Abstract: Biopharmaceuticals, such as proteins, peptides, nucleic acids and vaccines, bring about great hopes for the prevention and treatment of various diseases, but the industrialization of these products still faces challenges such as structural instability, inefficient bioactivity and low bioavailability. Ionic liquids (ILs), the marvelous solvent media with inimitable and tunable properties, may provide alternative solutions to overcome the above problems of biopharmaceutical industry. Progress has gradually been made through studies by combination of ILs with biomacromolecules. The applications involved the stabilization, protection, and delivery of biopharmaceuticals. Recent trends are being forwarded to using ILs in vaccines and nucleic acid drugs. However, challenges remain on the toxicity and safety issues. Besides, the cost of adding ILs to the benefits of biopharmaceuticals need to be considered.

Key words: Ionic liquids, Biopharmaceutical engineering, Biomacromolecules, Stabilization, Vaccine, Delivery

摘要： Biopharmaceuticals, such as proteins, peptides, nucleic acids and vaccines, bring about great hopes for the prevention and treatment of various diseases, but the industrialization of these products still faces challenges such as structural instability, inefficient bioactivity and low bioavailability. Ionic liquids (ILs), the marvelous solvent media with inimitable and tunable properties, may provide alternative solutions to overcome the above problems of biopharmaceutical industry. Progress has gradually been made through studies by combination of ILs with biomacromolecules. The applications involved the stabilization, protection, and delivery of biopharmaceuticals. Recent trends are being forwarded to using ILs in vaccines and nucleic acid drugs. However, challenges remain on the toxicity and safety issues. Besides, the cost of adding ILs to the benefits of biopharmaceuticals need to be considered.

关键词: Ionic liquids, Biopharmaceutical engineering, Biomacromolecules, Stabilization, Vaccine, Delivery

Xuan Lin, Zhiguo Su, Yanli Yang, Songping Zhang. The potential of ionic liquids in biopharmaceutical engineering[J]. Chinese Journal of Chemical Engineering, 2021, 29(2): 236-243.

Xuan Lin, Zhiguo Su, Yanli Yang, Songping Zhang. The potential of ionic liquids in biopharmaceutical engineering[J]. 中国化学工程学报, 2021, 29(2): 236-243.

References

[1] F. He, G.W. Becker, J.R. Litowski, L.O. Narhi, D.N. Brems, V.I. Razinkov, Highthroughput dynamic light scattering method for measuring viscosity of concentrated protein solutions, Anal. Biochem. 399 (1) (2010) 141–143.
[2] A. Banerjee, K. Ibsen, Y. Iwao, M. Zakrewsky, S. Mitragotri, Transdermal protein delivery using choline and geranate (CAGE) deep eutectic solvent, Adv. Healthcare Mater. 6 (15) (2017) 1601411.
[3] A. Banerjee, K. Ibsen, T. Brown, R. Chen, C. Agatemor, S. Mitragotri, Ionic liquids for oral insulin delivery, Proc. Natl. Acad. Sci. USA 115 (28) (2018) 201722338.
[4] H. Zhao, Methods for stabilizing and activating enzymes in ionic liquids-a review, J. Chem. Technol. Biotechnol. 85 (7) (2010) 891–907.
[5] M. Smiglak, J.M. Pringle, X. Lu, L. Han, S. Zhang, H. Gao, D.R. MacFarlane, R.D. Rogers, Ionic liquids for energy, materials, and medicine, Chem. Commun. 50 (66) (2014) 9228–9250.
[6] Z. Sidat, T. Marimuthu, P. Kumar, L.C. du Toit, P.P.D. Kondiah, Y.E. Choonara, V. Pillay, Ionic liquids as potential and synergistic permeation enhancers for transdermal drug delivery, Pharmaceutics 11 (2) (2019) 96.
[7] W.L. Hough, M. Smiglak, H. Rodriguez, R.P. Swatloski, S.K. Spear, D.T. Daly, J. Pernak, J.E. Grisel, R.D. Carliss, M.D. Soutullo, J.H. Davis, R.D. Rogers, The third evolution of ionic liquids: active pharmaceutical ingredients, New J. Chem. 31 (8) (2007) 1429–1436.
[8] W.Z. Huang, X.Y. Wu, J.P. Qi, Q.G. Zhu, W. Wu, Y. Lu, Z.J. Chen, Ionic liquids: green and tailor-made solvents in drug delivery, Drug Discovery Today 25 (5) (2020) 901–908.
[9] N. Adawiyah, M. Moniruzzaman, S. Hawatulailaa, M. Goto, Ionic liquids as a potential tool for drug delivery systems, MedChemComm 7 (10) (2016) 1881–1897.
[10] J. Wang, Y.Q. Tang, H.Y. Chu, J.W. Shen, C.Z. Wang, Y.M. Wei, Adjusting the chromatographic properties of poly(ionic liquid) -modified stationary phases by substitution on the imidazolium cation, J. Sep. Sci. 43 (14) (2020) 2737–2958.
[11] J.L. Shamshina, S.P. Kelley, G. Gurau, R.D. Rogers, Develop ionic liquid drugs, Nature 528 (7581) (2015) 188–189.
[12] C. Mukesh, D. Mondal, M. Sharma, K. Prasad, Rapid dissolution of DNA in a novel bio-based ionic liquid with long-term structural and chemical stability: Successful recycling of the ionic liquid for reuse in the process, Chem. Commun. 49 (61) (2013) 6849–6851.
[13] D.M. Foureau, R.M. Vrikkis, C.P. Jones, K.D. Weaver, D.R. MacFarlane, J.C. Salo, I. H. McKillop, G.D. Elliott, In vitro assessment of choline dihydrogen phosphate (CDHP) as a vehicle for recombinant human interleukin-2 (rhIL-2), Cell. Mol. Bioeng. 5 (4) (2012) 390–401.
[14] A. Kumar, P. Venkatesu, The stability of insulin in the presence of short alkyl chain imidazolium-based ionic liquids, RSC Adv. 4 (9) (2014) 4487–4499.
[15] M. Reslan, V. Ranganathan, D.R. Macfarlane, V. Kayser, Choline ionic liquid enhances the stability of Herceptin (R) (trastuzumab), Chem. Commun. 54 (75) (2018) 10622–10625.
[16] S. Araki, R. Wakabayashi, M. Moniruzzaman, N. Kamiya, M. Goto, Ionic liquidmediated transcutaneous protein delivery with solid-in-oil nanodispersions, MedChemComm 6 (12) (2015) 2124–2128.
[17] M. Mahkam, F. Hosseinzadeh, M. Galehassadi, Preparation of ionic liquid functionalized silica nanoparticles for oral drug delivery, J. Biomater. Nanobiotechnol. 3 (3) (2012) 391–395.
[18] S.V. Dzyuba, R.A. Bartsch, New room-temperature ionic liquids with C-2-symmetrical imidazolium cations, Chem. Commun. 16 (2001) 1466–1467.
[19] S. Keskin, D. Kayrak-Talay, U. Akman, O. Hortacsu, A review of ionic liquids towards supercritical fluid applications, J. Supercrit. Fluids 43 (1) (2007) 150–180.
[20] R.M. Vrikkis, K.J. Fraser, K. Fujita, D.R. MacFarlane, G.D. Elliott, Biocompatible ionic liquids: a new approach for stabilizing proteins in liquid formulation, J. Biomech. Eng-T. Asme. 131 (7) (2009) 074514.
[21] K.D. Weaver, H.J. Kim, J. Sun, D.R. MacFarlane, G.D. Elliott, Cyto-toxicity and biocompatibility of a family of choline phosphate ionic liquids designed for pharmaceutical applications, Green Chem. 12 (3) (2010) 507–513.
[22] M. Vranes, A. Tot, S. Papovic, D. Cetojevic-Simin, S. Markov, A. Velicanski, M. Popsavin, S. Gadzuric, Physicochemical features and toxicity of some vitamin based ionic liquids, J. Mol. Liq. 247 (2017) 411–424.
[23] W.X. Li, L. Zhu, Z.K. Du, B. Li, J.H. Wang, J. Wang, C. Zhang, L.S. Zhu, Acute toxicity, oxidative stress and DNA damage of three task-specific ionic liquids ([C(2) NH(2) MIm]BF4, [MOEMIm]BF4, and [HOEMIm]BF4) to zebrafish (Danio rerio), Chemosphere 249 (2020) 126119.
[24] K. Bakshi, S. Mitra, V.K. Sharma, M.S.K. Jayadev, V.G. Sakai, R. Mukhopadhyay, A. Gupta, S.K. Ghosh, Imidazolium-based ionic liquids cause mammalian cell death due to modulated structures and dynamics of cellular membrane, Biochim. Biophys. Acta, Biomembr. 1862 (2) (2020) 183103.
[25] A.A.C.T. Hijo, H.D.F.Q. Barros, G.J. Maximo, C.B.B. Cazarin, L.B.E. da Costa, J.F.B. Pereira, M.R. Marostica, A.J.A. Meirelles, Subacute toxicity assessment of biobased ionic liquids in rats, Food Res. Int. 134 (2020) 109125.
[26] M. Guncheva, P. Ossowicz, E. Janus, S. Todinova, D. Yancheva, Elucidation of the effect of some cholinium amino acid ionic liquids on the thermal and the conformational stability of insulin, J. Mol. Liq. 283 (1) (2019) 257–262.
[27] R. Vijayaraghavan, A. Izgorodin, V. Ganesh, M. Surianarayanan, D.R. MacFarlane, Long-term structural and chemical stability of DNA in hydrated ionic liquids, Angew. Chem., Int. Ed. 49 (9) (2010) 1631–1633.
[28] B. Jagannath, S. Muthukumar, S. Prasad, Electrical double layer modulation of hybrid room temperature ionic liquid/aqueous buffer interface for enhanced sweat based biosensing, Anal. Chim. Acta 1016 (3) (2018) 29–39.
[29] X. Lin, Y. Yang, S. Li, Y.M. Song, G.H. Ma, Z.G. Su, S.P. Zhang, Unique stabilizing mechanism provided by biocompatible choline-based ionic liquids for inhibiting dissociation of inactivated foot-and-mouth disease virus particles, RSC Adv. 9 (24) (2019) 13933–13939.
[30] X.Y. Wu, Z.J. Chen, Y. Li, Q. Yu, Y. Lu, Q.G. Zhu, Y. Li, D.P. An, J.P. Qi, W. Wu, Improving dermal delivery of hydrophilic macromolecules by biocompatible ionic liquid based on choline and malic acid, Int. J. Pharm. 558 (10) (2019) 380–387.
[31] P. Angsantikul, K.V. Peng, A.M. Curreri, Y. Chua, K.V.Z. Chen, J. Ehondor, S. Mitragotri, Ionic liquids and deep eutectic solvents for enhanced delivery of antibodies in the gastrointestinal tract, Adv. Funct. Mater. 2002912 (2020), https://doi.org/10.1002/adfm.202002912.
[32] K. Peng, Y. Shi, A. LaBarbiera, S. Mitragotri, Mucoadhesive ionic liquid gel patches for oral delivery, ACS Biomater. Sci. Eng. (2020), https://doi.org/10.1021/acsbiomaterials.0c01024.
[33] V. Dharamdasani, A. Mandal, Q.M. Qi, I. Suzuki, M.V.L.B. Bentley, S. Mitragotri, Topical delivery of siRNA into skin using ionic liquids, J. Controlled Release 323 (10) (2020) 475–482.
[34] A. Kumar, P. Venkatesu, Prevention of insulin self-aggregation by a protic ionic liquid, RSC Adv. 3 (2) (2013) 362–367.
[35] S. Todinova, M. Guncheva, D. Yancheva, Thermal and conformational stability of insulin in the presence of imidazolium-based ionic liquids, J. Therm. Anal. Calorim. 123 (3) (2016) 2591–2598.
[36] A. Kumar, P. Venkatesu, Does the stability of proteins in ionic liquids obey the Hofmeister series?, Int. J. Biol. Macromol. 63 (2014) 244–253.
[37] H. Weingartner, C. Cabrele, C. Herrmann, How ionic liquids can help to stabilize native proteins, Phys. Chem. Chem. Phys. 14 (2) (2012) 415–426.
[38] R. Patel, M. Kumari, A.B. Khan, Recent advances in the applications of ionic liquids in protein stability and activity: A review, Appl. Biochem. Biotechnol. 172 (8) (2014) 3701–3720.
[39] J.V. Rodrigues, V. Prosinecki, I. Marrucho, L.P. Rebelo, C.M. Gomes, Protein stability in an ionic liquid milieu: on the use of differential scanning fluorimetry, Phys. Chem. Chem. Phys. 13 (30) (2011) 13614–13616.
[40] P. Attri, P. Venkatesu, A. Kumar, Activity and stability of alpha-chymotrypsin in biocompatible ionic liquids: enzyme refolding by triethyl ammonium acetate, Phys. Chem. Chem. Phys. 13 (7) (2011) 2788–2796.
[41] K. Fujita, D.R. MacFarlane, M. Forsyth, Protein solubilising and stabilising ionic liquids, Chem. Commun. 38 (38) (2005) 4804–4806.
[42] S.N. Baker, T.M. McCleskey, S. Pandey, G.A. Baker, Fluorescence studies of protein thermostability in ionic liquids, Chem. Commun. 10 (8) (2004) 940–941.
[43] N. Byrne, B. Rodoni, F. Constable, S. Varghese, J.H. Davis Jr., Enhanced stabilization of the tobacco mosaic virus using protic ionic liquids, Phys. Chem. Chem. Phys. 14 (29) (2012) 10119–10121.
[44] F. Geng, L.Q. Zheng, J. Liu, L. Yu, C.H. Tung, Interactions between a surface active imidazolium ionic liquid and BSA, Colloid Polym. Sci. 287 (11) (2009) 1253–1259.
[45] P. Attri, P. Venkatesu, Influence of protic ionic liquids on the structure and stability of succinylated Con A, Int. J. Biol. Macromol. 51 (1–2) (2012) 119–128.
[46] K. Fujita, M. Forsyth, D.R. MacFarlane, R.W. Reid, G.D. Elliott, Unexpected improvement in stability and utility of cytochrome c by solution in biocompatible ionic liquids, Biotechnol. Bioeng. 94 (6) (2006) 1209–1213.
[47] S.W. Bae, W.J. Chang, Y.M. Koo, S.H. Ha, Enhanced refolding of lysozyme with imidazolium-based room temperature ionic liquids: Effect of hydrophobicity and sulfur residue, Sci. China: Chem. 55 (8) (2012) 1657–1662.
[48] P. Attri, P. Venkatesu, A. Kumar, N. Byrne, A protic ionic liquid attenuates the deleterious actions of urea on a-chymotrypsin, Phys. Chem. Chem. Phys. 13 (38) (2011) 17023.
[49] H. Zhao, G.A. Baker, Z. Song, O. Olubajo, T. Crittle, D. Peters, Designing enzymecompatible ionic liquids that can dissolve carbohydrates, Green Chem. 10 (6) (2008) 696–705.
[50] K.D. Weaver, R.M. Vrikkis, M.P. Van Vorst, J. Trullinger, R. Vijayaraghavan, D.M. Foureau, I.H. McKillop, D.R. MacFarlane, J.K. Krueger, G.D. Elliott, Structure and function of proteins in hydrated choline dihydrogen phosphate ionic liquid, Phys. Chem. Chem. Phys. 14 (2) (2012) 790–801.
[51] H. Kaplon, J.M. Reichert, Antibodies to watch in 2018, Mabs-Austin 10 (2) (2018) 183–203.
[52] F. He, C.E. Woods, E. Trilisky, K.M. Bower, J.R. Litowski, B.A. Kerwin, G.W. Becker, L.O. Narhi, V.I. Razinkov, Screening of monoclonal antibody formulations based on high-throughput thermostability and viscosity measurements: design of experiment and statistical analysis, J. Pharm. Sci. 100 (4) (2011) 1330–1340.
[53] C.A. Summers, R.A. Flowers, Protein renaturation by the liquid organic salt ethylammonium nitrate, Protein Sci. 9 (10) (2000) 2001–2008.
[54] M. Bisht, P. Venkatesu, Influence of cholinium-based ionic liquids on the structural stability and activity of alpha-chymotrypsin, New J. Chem. 41 (22) (2017) 13902–13911.
[55] L. Xue, J.N. Liu, Q. Wang, C. Zhang, L.F. Xu, J. Luo, J. Wang, C. Qin, Y.D. Liu, Z.G. Su, Purification and assembling a fused capsid protein as an enterovirus 71 vaccine candidate from inclusion bodies to pentamer-based nanoparticles, Biochem. Eng. J. 117 (15) (2017) 139–146.
[56] Y.J. Ma, R.J.M. Nolte, J.J.L.M. Cornelissen, Virus-based nanocarriers for drug delivery, Adv. Drug Delivery Rev. 64 (9) (2012) 811–825.
[57] F. Caridi, A. Vazquez-Calvo, B. Borrego, K. McCullough, A. Summerfield, F. Sobrino, M.A. Martin-Acebes, Preserved immunogenicity of an inactivated vaccine based on foot-and-mouth disease virus particles with improved stability, Vet. Microbiol. 203 (2017) 275–279.
[58] Y.L. Yang, Q.Z. Zhao, Z.J. Li, L.J. Sun, G.H. Ma, S.P. Zhang, Z.G. Su, Stabilization study of inactivated foot and mouth disease virus vaccine by size-exclusion HPLC and differential scanning calorimetry, Vaccine 35 (18) (2017) 2413–2419.
[59] M.M. Harmsen, H.P. Fijten, D.F. Westra, A. Dekker, Stabilizing effects of excipients on dissociation of intact (146S) foot-and-mouth disease virions into 12S particles during storage as oil-emulsion vaccine, Vaccine 33 (21) (2015) 2477–2484.
[60] F.M. Ellard, J. Drew, W.E. Blakemore, D.I. Stuart, A.M.Q. King, Evidence for the role of His-142 of protein 1C in the acid-induced disassembly of foot-andmouth disease virus capsids, J. Gen. Virol. 80 (8) (1999) 1911–1918.
[61] H. Yoshiura, M. Tamura, M. Aso, N. Kamiya, M. Goto, Ionic liquid-in-oil microemulsions as potential carriers for the transdermal delivery of methotrexate, J. Chem. Eng. Jpn. 46 (11) (2013) 794–796.
[62] R. Islam, R. Chowdhury, R. Wakabayashi, Y. Tahara, N. Kamiya, M. Moniruzzaman, M. Goto, Choline and amino acid based biocompatible ionic liquid mediated transdermal delivery of the sparingly soluble drug acyclovir, Int. J. Pharm. 582 (30) (2020) 119335.
[63] M.R. Islam, M.R. Chowdhury, R. Wakabayashi, N. Kamiya, M. Moniruzzaman, M. Goto, Ionic liquid-in-oil microemulsions prepared with biocompatible choline carboxylic acids for improving the transdermal delivery of a sparingly soluble drug, Pharmaceutics 12 (4) (2020) 392.
[64] L.Y. Zheng, Z.Y. Zhao, Y. Yang, Y.M. Li, C.X. Wang, Novel skin permeation enhancers based on amino acid ester ionic liquid: Design and permeation mechanism, Int. J. Pharm. 576 (25) (2020) 119031.
[65] C. Agatemor, K.N. Ibsen, E.E.L. Tanner, S. Mitragotri, Ionic liquids for addressing unmet needs in healthcare, Bioeng. Transl. Med. 3 (1) (2018) 7–25.
[66] N. Kundu, S. Roy, D. Mukherjee, T.K. Maiti, N. Sarkar, Unveiling the interaction between fatty-acid-modified membrane and hydrophilic imidazolium-based ionic liquid: understanding the mechanism of ionic liquid cytotoxicity, J. Phys. Chem. B 121 (34) (2017) 8162–8170.
[67] P. Drucker, A. Ruhling, D. Grill, D. Wang, A. Draeger, V. Gerke, F. Glorius, H.J. Galla, Imidazolium salts mimicking the structure of natural lipids exploit remarkable properties forming lamellar phases and giant vesicles, Langmuir 33 (6) (2017) 1333–1342.
[68] Y. Tahara, S. Honda, N. Kamiya, H. Piao, A. Hirata, E. Hayakawa, T. Fujii, M. Goto, A solid-in-oil nanodispersion for transcutaneous protein delivery, J. Controlled Release 131 (1) (2008) 14–18.
[69] L.R. Jorge, L.K. Harada, E.C. Silva, W.F. Campos, F.C. Morelli, G. Shimamoto, J.F.B. Pereira, J.M. Oliveira, M. Tubino, M.M.D.C. Vila, V.M. Balcao, Non-invasive transdermal delivery of human insulin using ionic liquids: In vitro studies, Front. Pharmacol. 11 (2020) 243.
[70] V.E.J.C. Schijns, E.C. Lavelle, Trends in vaccine adjuvants, Expert Rev. Vaccines 10 (4) (2011) 539–550.
[71] A.S. McKee, P. Marrack, Old and new adjuvants, Curr. Opin. Immunol. 47 (2017) 44–51.
[72] M. Moniruzzaman, Y. Tahara, M. Tamura, N. Kamiya, M. Goto, Ionic liquidassisted transdermal delivery of sparingly soluble drugs, Chem. Commun. 46 (9) (2010) 1452–1454.
[73] S. Chadwick, C. Kriegel, M. Amiji, Nanotechnology solutions for mucosal immunization, Adv. Drug Delivery Rev. 62 (4–5) (2010) 394–407.
[74] J. Chen, F.W. Xie, X.X. Li, L. Chen, Ionic liquids for the preparation of biopolymer materials for drug/gene delivery: a review, Green Chem. 20 (18) (2018) 4169–4200.
[75] I.F. Mena, E. Diaz, J. Palomar, J.J. Rodriguez, A.F. Mohedano, Cation and anion effect on the biodegradability and toxicity of imidazolium-and choline-based ionic liquids, Chemosphere 240 (2020) 124947.
[76] S.G. Wu, F.F. Li, L.B. Zeng, C.Y. Wang, Y.R. Yang, Z.J. Tan, Assessment of the toxicity and biodegradation of amino acid-based ionic liquids, RSC Adv. 9 (18) (2019) 10100–10108.
[77] M.U. Shah, M. Moniruzzaman, M.M.R. Talukder, S.B. Yusup, Antimicrobial activity and acute toxicity of choline based ionic liquid mixtures, Mater. Today: Proc. 19 (4) (2019) 1309–1314.
[78] M. Uddin, D. Basak, R. Hopefl, B. Minofar, Potential application of ionic liquids in pharmaceutical dosage forms for small molecule drug and vaccine delivery system, J. Pharm. Pharm. Sci. 23 (2020) 158–176.
[79] P. Yoganantharajah, D.J. Eyckens, J.L. Pedrina, L.C. Henderson, Y. Gibert, A study on acute toxicity and solvent capacity of solvate ionic liquids in vivo using a zebrafish model (Danio rerio), New J. Chem. 40 (8) (2016) 6599–6603.
[80] S. Stolte, J.r. Arning, U. Bottin-Weber, M. Matzke, F. Stock, K. Thiele, M. Uerdingen, U. Welz-Biermann, B. Jastorff, J. Ranke, Anion effects on the cytotoxicity of ionic liquids, Green Chem. 8 (7) (2006) 621–629.
[81] A. Mandal, N. Kumbhojkar, C. Reilly, V. Dharamdasani, A. Ukidve, D.E. Ingber, S. Mitragotri, Treatment of psoriasis with NFKBIZ siRNA using topical ionic liquid formulations, Sci. Adv. 6 (30) (2020)eabb6049.