RT Journal Article T1 A ready-to-use dry powder formulation based on protamine nanocarriers for pulmonary drug delivery A1 Robla Álvarez, Sandra A1 Varela Calviño, Rubén A1 Ambrus, Rita A1 Csaba, Noemi Stefania K1 Protamine nanocapsules K1 Rifabutin K1 Mannitol K1 Pulmonary drug delivery K1 Anti-tuberculotic treatment AB 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 PB Elsevier YR 2023 FD 2023 LK http://hdl.handle.net/10347/30627 UL http://hdl.handle.net/10347/30627 LA eng NO European Journal of Pharmaceutical Sciences 185 (2023) 106442 NO This research was funded by Ministerio de Ciencia e Innovacion RETOS - PID2019-107500RB-I00, Ministry of Human Capacities, Hungary grant TKP2021-EGA-32 and the Erasmus+ program of the European Union DS Minerva RD 24 abr 2026