Metal–Organic Framework Synthesis Strategies for Efficient Encapsulation and Sustained Release of Bioactive Compounds

Metal–organic frameworks (MOFs) have emerged as versatile carriers for biomedical applications because of their tunable porosity, high surface area, and structural robustness. Their biocompatibility depends on carefully selecting nontoxic metals such as Fe, Zn, or Mg; safe organic ligands, including carboxylates, imidazolates, and pyridines; and stabilizing coatings such as polyethylene glycol (PEG), chitosan, and polyvinylpyrrolidone (PVP) that enhance aqueous stability and enable controlled release. Conventional synthesis methods typically yield highly crystalline frameworks but require long reaction times and extensive solvent use. In contrast, nonconventional approaches are gaining popularity for their faster, energy‐efficient methods. Techniques such as microwave irradiation, sonochemical activation, and electrochemical synthesis provide rapid, controllable conditions that reduce energy consumption and shorten reaction times. In particular, mechanochemical encapsulation is an eco‐friendly, sustainable, scalable, and high‐yield methodology that enables in situ entrapment of bioactive molecules and enhances adsorption capacity. Moreover, the mechanochemical methodology enables modulation of physicochemical parameters such as morphology and particle size, which critically influence adsorption behavior and host–guest interactions. Examples of encapsulation processes involving antidiabetic agents, anticancer therapeutics, and antioxidants are presented, and these can be translated into mechanochemical approaches. In this regard, MOFs stand out as promising platforms for targeted delivery and sustained release. Integrating rational component selection, coating strategies, and sustainable synthesis methodologies positions MOFs as next‐generation biocompatible carriers for precision biomedical applications.