Preparation and characterization of siRNA-containing microspheres intended for inhalation with mannitol and albumin using spray drying technique

Abstract

Despite the promising results of pulmonary delivery of naked siRNA, studies focusing on inhaled formulations of nucleic acids are lacking. Liquid-based formulations were used in most of the investigations, which is not desirable since biomolecules are typically prone to hydrolysis. The lack of dedicated powder formulation thus accounted for one of the major obstacles hindering the clinical applications of siRNA therapeutics to treat pulmonary diseases. This study aimed to explore the feasibility of co-spray drying siRNA (at 0.75% w/w) with mannitol, which served as a bulking agent. Bovine serum albumin (BSA) or human serum albumin (HSA) at 10% w/w were included in some formulations to investigate its potential to improve particle dispersion. Integrity of siRNA was preserved upon spray drying as studied by gel electrophoresis. In vitro aerosolization performance evaluated using the Next Generation Impactor coupled with a low resistance model inhaler (Osmohaler®) showed that the fine particle fraction (< 5 µm) of siRNA powders loaded with 10% BSA or HSA was 62.1% and 58.6% respectively, as compared to 56% when albumin was absent. Interestingly, the FPF of the protein-containing siRNA powders reached above 70% when dispersed at a reduced flow rate. This study showed that co-spray drying siRNA with albumin could improve the aerosolization performance of the powder.