Ginkgolide B-cyclodextrin inclusion complexes: an encapsulation strategy for improved solubility and aerosol inhalation therapy in bronchial asthma.

Bronchial asthma represents a long-term inflammatory reaction in the airways, marked by the accumulation of eosinophils. Ginkgolide B (GB), derived from ginkgo biloba, serves as a potent natural antagonist of platelet activating factor (PAF). It can greatly reduce the production and release of eosinophils while minimizing the infiltration of other inflammatory cells in the airways, thus contributing to the management of bronchial asthma. However, due to its low bioavailability caused by poor water solubility and inherent bitter taste, it's hard for Ginkgolide B to meet the standards required for effective treatment of asthma. In this study, we developed two cyclodextrin derivatives of Ginkgolide B, namely GB-SBE-β-CD and GB-HP-γ-CD, for the therapy of bronchial asthma through aerosol inhalation. Both SBE-β-CD and HP-γ-CD effectively capsulated the Ginkgolide B. Molecular docking analysis revealed the spatial structure of GB-SBE-β-CD and GB-HP-γ-CD, highlighting hydrogen bonding as the primary driving force behind their formation. In vitro cell assays demonstrated that both Ginkgolide B and Ginkgolide B-cyclodextrin inclusion compounds exhibited good safety and potent anti-inflammatory activity. In addition, inhalation of aerosolized GB-SBE-β-CD and GB-HP-γ-CD markedly alleviated the symptoms of OVA-induced asthma in BALB/c mice, lowering infiltration of inflammatory cells, and significantly contributing to asthma treatment. The current findings suggest that the inhalation of Ginkgolide B-cyclodextrin represents a safe and promising option for managing bronchial asthma.