Development of a stable inhalable dry powder formulation with osteoglycin fragment for alveolar epithelial repair

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and progressive lung function decline, with a critical need for innovative treatments that can repair damaged lung tissue. The active fragment of osteoglycin (OGN) has previously shown significant regenerative potential in activating growth of alveolar epithelial cells, making it a promising candidate for therapeutic development. In this study, we developed an inhalable dry powder formulation of the OGN fragment using spray drying, incorporating inulin or mannitol as excipients and leucine as a dispersion enhancer. The formulations were assessed for their ability to support lung organoid formation and differentiation in vitro. After spray drying with inulin or mannitol, the OGN fragment maintained its ability to induce organoid formation, but only the formulation containing inulin supported the differentiation towards alveolar-type organoids (surfactant protein C positive). After 28 days of storage at high temperatures (60 °C) inulin was found to provide superior stability compared to mannitol. The dry powder formulation with OGN fragment and inulin demonstrated favorable aerodynamic properties, meeting the requirements for deep lung deposition when dispersed via a dry powder inhaler. Additionally, we showed that adding 4 % leucine or inulin sweeper particles significantly improved the dispersion behavior of the formulation and reduced dry powder inhaler retention. This study highlights the potential of an inhalable OGN fragment formulation as a novel therapeutic approach for lung tissue repair in COPD. The findings support further development and clinical evaluation of this formulation, particularly with inulin as the preferred stabilizing excipient.