Asiatic acid cyclodextrin inclusion micro-cocrystal for insoluble drug delivery and acute lung injury therapy enhancement

J Nanobiotechnology. 2024 Mar 17;22(1):119. doi: 10.1186/s12951-024-02387-7.

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.

Keywords: Acute lung injury; Asiatic acid; Inclusion cocrystal; Lung targeting delivery; Spring-and-hover model.

MeSH terms

  • Acute Lung Injury* / drug therapy
  • Cyclodextrins* / chemistry
  • Drug Delivery Systems
  • Humans
  • Pentacyclic Triterpenes*
  • Solubility
  • Tissue Distribution

Substances

  • Cyclodextrins
  • asiatic acid
  • Pentacyclic Triterpenes