Inhalation Properties and Stability of Nebulized Naked siRNA Solution for Pulmonary Therapy

• Published in: Chemical & pharmaceutical bulletin Vol. 64; no. 1; pp. 63 - 67
• Main Authors: Tahara, Kohei, Hashimoto, Wakana, Takeuchi, Hirofumi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.01.2016; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Administration, Inhalation; aerodynamic particle size; Aerosols - administration & dosage; Aerosols - chemistry; Aerosols - therapeutic use; contact angle; Electrophoresis, Agar Gel; Humans; Lung Diseases - drug therapy; Nebulizers and Vaporizers; Particle Size; Pharmaceutical Solutions - administration & dosage; Pharmaceutical Solutions - chemistry; Pharmaceutical Solutions - therapeutic use; Polymers - administration & dosage; Polymers - chemistry; Polymers - therapeutic use; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - chemistry; RNA, Small Interfering - therapeutic use; small interfering RNA (siRNA); Surface Tension; vibrating-mesh nebulizer
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c15-00615

The use of naked unmodified small interfering RNA (N-siRNA) without vector has previously been investigated as a pulmonary therapy. However, little is known regarding stabilities and aerodynamic particle sizes of N-siRNA-containing droplets; nebulizers have not yet been optimized for N-siRNA solutions. Thus, in this study, we investigated the feasibility of inhaled N-siRNA solutions for pulmonary therapy using nebulization. Various nebulizers and N-siRNA concentrations were assessed in terms of siRNA integrity after nebulization, and inhalation properties including aerodynamic particle size were examined. In comparison with ultrasonic-, air-jet-, and vibrating-mesh nebulizers, N-siRNA integrity was not affected by nebulization. Thus, in further experiments, performances of N-siRNA aerosols with different nebulizers and N-siRNA concentrations were evaluated and screened using an aerodynamic particle sizer (APS) which employed the time-of-flight principle or a cascade impactor. Mean mass aerodynamic diameters of N-siRNA-containing droplets from vibrating-mesh nebulizers tended to decrease with increasing N-siRNA concentrations, reflecting the influence of N-siRNA solutions on surface tension, as indicated by contact angles. These data indicate the utility of APS instruments for investigating the nebulized characteristics of expensive drugs including siRNAs and may facilitate the development of N-siRNA inhalation formulations.