Cyclodextrin-Based Metal-Organic Frameworks for Pulmonary Delivery of Curcumin with Improved Solubility and Fine Aerodynamic Performance

Abstract Pulmonary drug delivery has attracted considerable attention in recent years. However, it is still a major challenge to deliver poorly water-soluble drugs to lungs with good solubility and fine aerodynamic performance. In this study, curcumin was loaded into cyclodextrin-based metal-organic frameworks (CD-MOFs) for pulmonary delivery. Compared with micronized curcumin prepared by jet milling, curcumin-loaded CD-MOFs (Cur-CD-MOFs) exhibited excellent aerodynamic performance, which was attributed to the unique porous structure and lower density of CD-MOFs. The dissolution test showed that the drug release rate of Cur-CD-MOFs was much faster than that of micronized curcumin. The all-atom molecular dynamic simulation showed that curcumin molecules were loaded into the hydrophobic cavities of CD-MOFs or entered into the large hydrophilic cavities to form nanoclusters. The elevated wettability of Cur-CD-MOFs and the unique spatial distribution feature of curcumin in porous interior of CD-MOFs might be favorable for the improved dissolution rate. The DPPH radical scavenging test showed that Cur-CD-MOFs had prominent antioxidant activities. Therefore, CD-MOFs were expected to be promising carriers for pulmonary delivery of poorly water-soluble drugs.