A Pilot Study Exploiting the Industrialization Potential of Solid Lipid Nanoparticle-Based Metered-Dose Inhalers

Abstract

Delivery of inhalable nanoparticles through metered-dose inhalers (MDI) is a promising approach to treat lung disease such as asthma and chronic obstructive pulmonary disease. Nanocoating of the inhalable nanoparticles helps in stability and cellular uptake enhancement but complicates the production process. Thus, it is meaningful to accelerate the translation process of MDI encapsulating inhalable nanoparticles with nanocoating structure. In this study, solid lipid nanoparticles (SLN) are selected as a model inhalable nanoparticle system. An established reverse microemulsion strategy was utilized to explore the industrialization potential of SLN-based MDI. Three categories of nanocoating with the functions of stabilization (by Poloxamer 188, encoded as SLN(0)), cellular uptake enhancement (by cetyltrimethylammonium bromide, encoded as SLN(+)), and targetability (by hyaluronic acid, encoded as SLN(-)) were constructed upon SLN, whose particle size distribution and zeta-potential were characterized. Subsequently, SLN were loaded into MDI, and evaluated for the processing reliability, physicochemical nature, formulation stability, and biocompatibility. The results elucidated that three types of SLN-based MDI were successfully fabricated with good reproducibility and stability. Regarding safety, SLN(0) and SLN(-) showed negligible cytotoxicity on cellular level. This work serves as a pilot study for the scale-up of SLN-based MDI, and could be useful for the future development of inhalable nanoparticles.