AEROSOLIZATION OF RECOMBINANT INTERFERON GAMMA USING I-NEB-MINI JET NEBULIZER

ABSTRACT

TYPE TOPIC Pharmacotherapeutics PURPOSE: The i-NEB-MiniTM is a jet nebulizer designed for controlled delivery of small (< 2 mL) volumes of potent drugs to the deep lung. The purpose of this study was to determine aerosol parameters and post nebulization drug activity of a novel formulation of recombinant Interferon Gamma (rIFNγ), a pluripotent molecule with Th1 helper cell activity. METHODS: rINFγ (200 μg/mL) was aerosolized using i-NEB-MiniTM driven by a portable compressor at 3.5 L/min. Two (2) mL was aerosolized into a Next Generation Impactor (NGI) using a 15 L/min vacuum. Aerosol parameters (MMAD, GSD, Total Respirable Dose) were determined using an HPLC assay (Vectura Ltd., UK). Bioactivity pre-/post-nebulization was determined using an HLADR assay (PBL Assay Sciences, Piscataway, NJ, USA). RESULTS: The MMAD, GSD and Total Respirable dose from a 200 μg/mL formulation (n=6) was 2.5 (± 0.2), 1.6 (± 0.4) and 123.7 (± 19.8) μg respectively. The bioactivity pre- and post-nebulization was consistent with the EP standard suggesting that nebulization did not affect biological activity of the protein. CONCLUSIONS: This study indicates that a clinically relevant and reproducible dose of rINFγ can be delivered with i-NEB-MiniTM. Bioactivity assay indicates that aerosol rINFγ retains protein integrity after nebulization. CLINICAL IMPLICATIONS rINFγ is an immunomodulatory pleiotropic cytokine with potential for treatment of respiratory diseases such as Pulmonary Fibrosis, MDRTB, COPD and SARS-CoV-2. The results indicate that a clinically relevant dose of rINFγ can be aerosolized using the i-NEB-MiniTM jet nebulizer. DISCLOSURE Stony Brook and New York University hold patents on the use of inhaled interferon licensed to InspiRx, Inc. Dr. Smaldone consults to InspiRx and is a member of the advisory board. Mr. Shukla and Dr. Toddywala are employees of InspiRx. KEYWORD immunomodulation