A ready-to-use dry powder formulation based on protamine nanocarriers for pulmonary drug delivery

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, perme-ability, 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 asso-ciation 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. More-over, the aerodynamic evaluation showed a fine particle fraction deposition up to 30% and a mass median aerodynamic diameter of about 5 mu m, suitable for the pulmonary delivery of therapeutics.

Automated summary

To address the side effects and resistance issues of oral antibiotic therapy for respiratory diseases, inhalable formulations using biomaterials like protamine were developed to enhance therapeutic effect. Rifabutin-loaded protamine nanocapsules were prepared and evaluated for their physico-chemical characteristics, dissolution, permeability, stability, cytotoxicity, hemocompatibility, internalization, and aerodynamic properties. The nanocapsules showed good stability as suspension, both in storage and in biological media, as well as in the form of dry powder after lyophilization with mannitol. They exhibited excellent safety profile, cellular uptake, and compatibility with red blood cells. Furthermore, the aerodynamic evaluation demonstrated suitable particle size for pulmonary delivery of therapeutics, with a fine particle fraction deposition of up to 30% and a mass median aerodynamic diameter of about 5 µm.