Department of Bioprocess Engineering and Biotechnology, School of Pharmaceutical Sciences, São Paulo State University, CEP: 14801-902 Araraquara, SP, Brazil; Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, São Paulo University, CEP: 14040-020 Ribeirão Preto, SP, Brazil.
Escuela de Agronomía, Facultad de Ciencias Agronómicas y de los Alimentos, Pontificia Universidad Católica de Valparaíso, Quillota 2260000, Chile.
Biotechnol Adv. 2024 Mar-Apr;71:108316. doi: 10.1016/j.biotechadv.2024.108316. Epub 2024 Jan 8.
Biopharmaceuticals have allowed the control of previously untreatable diseases. However, their low solubility and stability still hinder their application, transport, and storage. Hence, researchers have applied different compounds to preserve and enhance the delivery of biopharmaceuticals, such as ionic liquids (ILs) and deep eutectic solvents (DESs). Although the biopharmaceutical industry can employ various substances for enhancing formulations, their effect will change depending on the properties of the target biomolecule and environmental conditions. Hence, this review organized the current state-of-the-art on the application of ILs and DESs to stabilize biopharmaceuticals, considering the properties of the biomolecules, ILs, and DESs classes, concentration range, types of stability, and effect. We also provided a critical discussion regarding the potential utilization of ILs and DESs in pharmaceutical formulations, considering the restrictions in this field, as well as the advantages and drawbacks of these substances for medical applications. Overall, the most applied IL and DES classes for stabilizing biopharmaceuticals were cholinium-, imidazolium-, and ammonium-based, with cholinium ILs also employed to improve their delivery. Interestingly, dilute and concentrated ILs and DESs solutions presented similar results regarding the stabilization of biopharmaceuticals. With additional investigation, ILs and DESs have the potential to overcome current challenges in biopharmaceutical formulation.
生物制药已使得原本无法治疗的疾病得到了控制。然而,其低溶解性和稳定性仍然阻碍了它们的应用、运输和储存。因此,研究人员已经应用了不同的化合物来保存和增强生物制药的递送,例如离子液体(ILs)和深共晶溶剂(DESs)。尽管生物制药行业可以使用各种物质来增强制剂,但它们的效果会根据目标生物分子的性质和环境条件而发生变化。因此,本综述组织了目前关于 ILs 和 DESs 在稳定生物制药方面的应用的最新技术,考虑了生物分子、ILs 和 DESs 类、浓度范围、稳定性类型和效果的性质。我们还针对 ILs 和 DESs 在药物制剂中的潜在利用进行了批判性讨论,考虑到该领域的限制,以及这些物质在医疗应用中的优缺点。总的来说,最常用于稳定生物制药的 IL 和 DES 类是胆碱、咪唑啉和铵基,胆碱 ILs 也被用于改善它们的递送。有趣的是,稀溶液和浓溶液的 ILs 和 DESs 在稳定生物制药方面呈现出相似的结果。随着进一步的研究,ILs 和 DESs 有可能克服生物制药制剂目前面临的挑战。