Robla Álvarez, SandraVarela Calviño, RubénAmbrus, RitaCsaba, Noemi Stefania2023-05-302023-05-302023European Journal of Pharmaceutical Sciences 185 (2023) 106442http://hdl.handle.net/10347/30627The 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 therapeuticseng© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)http://creativecommons.org/licenses/by/4.0/Protamine nanocapsulesRifabutinMannitolPulmonary drug deliveryAnti-tuberculotic treatmentinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107500RB-I00/ES/BIOMORPHIC PLATFORMS FOR THE PULMONARY DELIVERY OF NANOTHERAPEUTICSjournal article10.1016/j.ejps.2023.1064420928-0987open access