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- Title
Asiatic acid cyclodextrin inclusion micro-cocrystal for insoluble drug delivery and acute lung injury therapy enhancement.
- Authors
Shen, Huan; Pan, Li; Ning, Keke; Fang, Yuefei; Muhitdinov, Bahtiyor; Liu, Ergang; Huang, Yongzhuo
- Abstract
Background: Acute lung injury (ALI) is a fatal respiratory disease caused by overreactive immune reactions (e.g., SARS-CoV-2 infection), with a high mortality rate. Its treatment is often compromised by inefficient drug delivery barriers and insufficient potency of the currently used drugs. Therefore, developing a highly effective lung-targeted drug delivery strategy is a pressing clinical need. Results: In this study, the micro-sized inclusion cocrystal of asiatic acid/γ-cyclodextrin (AA/γCD, with a stoichiometry molar ratio of 2:3 and a mean size of 1.8 μm) was prepared for ALI treatment. The dissolution behavior of the AA/γCD inclusion cocrystals followed a "spring-and-hover" model, which meaned that AA/γCD could dissolve from the cocrystal in an inclusion complex form, thereby promoting a significantly improved water solubility (nine times higher than free AA). This made the cyclodextrin-based inclusion cocrystals an effective solid form for enhanced drug absorption and delivery efficiency. The biodistribution experiments demonstrated AA/γCD accumulated predominantly in the lung (Cmax = 50 µg/g) after systemic administration due to the micron size-mediated passive targeting effect. The AA/γCD group showed an enhanced anti-inflammatory therapeutic effect, as evidenced by reduced levels of pro-inflammatory cytokines in the lung and bronchoalveolar lavage fluids (BALF). Histological examination confirmed that AA/γCD effectively inhibited inflammation reactions. Conclusion: The micro-sized inclusion cocrystals AA/γCD were successfully delivered into the lungs by pulmonary administration and had a significant therapeutic effect on ALI.
- Subjects
LUNGS; CYCLODEXTRINS; LUNG injuries; BRONCHOALVEOLAR lavage; DRUG absorption; TREATMENT effectiveness; TABUN
- Publication
Journal of Nanobiotechnology, 2024, Vol 22, Issue 1, p1
- ISSN
1477-3155
- Publication type
Article
- DOI
10.1186/s12951-024-02387-7