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

Abstract 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.