Lipid/ZIF‐8 Biocomposites Based on Liposomes or Vesicles: In Situ Formation, and Preliminary Evaluation as Delivery Vehicles for Hydrophobic Drugs

Integrating lipid self-assemblies with metal-organic frameworks (MOFs) creates biocomposites ideal for encapsulation, protection, and delivery of functional species. This can be achieved using preformed MOFs or through in situ MOF formation. Herein, the one-pot formation of ZIF-8 MOF particles in the presence of two lipid self-assemblies (vesicles or liposomes) is reported, generating two types of hybrid lipid/ZIF-8 biocomposites. Each lipid assembly can be used to encapsulate hydrophobic actives into the hybrid lipid/ZIF-8 biocomposites, demonstrated with Nile Red and Astaxanthin (ATX) as representative cargo. In vitro digestion of ATX-loaded hybrid lipid/ZIF-8 particles in simulated intestinal fluid (SIF) shows distinct release kinetics: liposome-based particles offer a more sustained release compared to vesicle-based biocomposites. Intriguingly, in various media (water, simulated gastric fluid, bicarbonate, and SIF), the sodalite ZIF-8 topology in liposome-based lipid/ZIF-8 particles undergoes a crystalline phase transition to the denser, more-stable phase ZIF-C. This phase transition, along with a deeper internalization of ATX in liposome-based particles, accounts for the differences in release kinetics. In summary, the study provides valuable insights for the synthesis of hybrid lipid/ZIF-8 biocomposites, the encapsulation of hydrophobic molecules, the importance of investigating potential crystalline phase transitions of MOFs in different media, and their potential as drug delivery vehicles.