Spray-Dried Serum for Inhaled Antiviral Therapy

Background. Inhalable monoclonal antibodies were explored as therapeutics for respiratory viral infections due to their high specificity, which, however, can become a drawback if virus mutational escape occurs. Serum-derived polyclonal antibodies for prophylaxis reflect the diverse response of the immune system, reducing susceptibility to virus mutations and targeting multiple epitopes. Objectives. The aim of this work was the development of inhalable powders containing serum of rats immunized against SARS-CoV-2. Methods & Results. In a preliminary screening, combinations of sugar and an amino acid outperformed single excipients in terms of retention of protein size and residual moisture content. Four formulations were further developed on neat and albumin-depleted serum: HP beta CD/L-leucine in water, HP beta CD/L-leucine in phosphate buffer (KP), trehalose/L-leucine in water and HP beta CD/glycine in KP. These were subsequently evaluated for aerosol performance and protein stability. All spray-dried formulations afforded respirable particles (MMAD <= 5 mu m, FPF 70-80%), with L-leucine reducing hygroscopicity and particle aggregation while improving aerosol dispersibility. Conclusions. Albumin did not positively affect aerodynamic properties but provided greater protection of immunoglobulin activity (approximately 80% and 90% in albumin-depleted and neat serum, respectively). Buffer selection had no remarkable impact on the considered parameters. L-leucine with HP beta CD offered the best balance of aerodynamic performance and protein stabilization.