Robla Sandra, Varela Calviño Rubén, Ambrus Rita, Csaba Noemi
Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) and Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, A Coruña, Spain.
Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, A Coruña, Spain.
Eur J Pharm Sci. 2023 Jun 1;185:106442. doi: 10.1016/j.ejps.2023.106442. Epub 2023 Apr 3.
The use of oral antibiotic therapy for the treatment of respiratory diseases as tuberculosis has promoted the appearance of side effects as well as resistance to these treatments. The low solubility, high metabolism, and degradation of drugs as rifabutin, have led to the use of combined and prolonged therapies, which difficult patient compliance. In this work, we develop inhalable formulations from biomaterials such as protamine to improve the therapeutic effect. Rifabutin-loaded protamine nanocapsules (NCs) were prepared by solvent displacement method and were physico-chemically characterized and evaluated for their dissolution, permeability, stability, cytotoxicity, hemocompatibility, internalization, and aerodynamic characteristics after a spray-drying procedure. Protamine NCs presented a size of around 200 nm, positive surface charge, and drug association up to 54%. They were stable as suspension under storage, as well as in biological media and as a dry powder after lyophilization in the presence of mannitol. Nanocapsules showed a good safety profile and cellular uptake with no tolerogenic effect on macrophages and showed good compatibility with red blood cells. Moreover, the aerodynamic evaluation showed a fine particle fraction deposition up to 30% and a mass median aerodynamic diameter of about 5 µm, suitable for the pulmonary delivery of therapeutics.
将口服抗生素疗法用于治疗诸如肺结核之类的呼吸道疾病，已引发了副作用以及对这些治疗产生耐药性。药物如利福布汀的低溶解度、高代谢率和降解作用，导致了联合疗法和延长疗程的使用，这给患者的依从性带来困难。在这项研究中，我们利用鱼精蛋白等生物材料开发可吸入制剂，以提高治疗效果。通过溶剂置换法制备了载有利福布汀的鱼精蛋白纳米胶囊（NCs），并对其进行了物理化学表征，还评估了喷雾干燥过程后的溶解、渗透、稳定性、细胞毒性、血液相容性、内化和空气动力学特性。鱼精蛋白纳米胶囊的粒径约为200纳米，表面带正电荷，药物结合率高达54%。它们在储存时作为悬浮液稳定，在生物介质中稳定，在存在甘露醇的情况下冻干后作为干粉也稳定。纳米胶囊显示出良好的安全性和细胞摄取能力，对巨噬细胞没有致耐受性作用，并且与红细胞显示出良好的相容性。此外，空气动力学评估显示细颗粒分数沉积高达30%，质量中值空气动力学直径约为5微米，适合肺部给药治疗。
