Nanocochleates in Clinical Trials: A Review of Current Status, Challenges, and Future Directions.

Nanocochleates are novel lipid-based nanoparticles with a distinctive, multilayered, rolledup structure that resembles the spirals of a cochlea. They form when bivalent cations, such as calcium, interact with negatively charged lipid bilayers. These structures are gaining popularity in drug delivery due to their stability, biocompatibility, and ability to encapsulate and shield a wide range of bioactive substances, including hydrophobic drugs, peptides, and nucleic acids. Nanocochelates can withstand harsh environmental conditions, such as acidic pH or enzymatic degradation, making them suitable carriers for oral, injectable, and transdermal medication administration. Their unique construction enables the gradual release of encapsulated medicines, thereby increasing bioavailability and therapeutic effectiveness. Additionally, nanocochleates can target specific tissues or cells, allowing for precision medical methods. A recent study demonstrates their promise for overcoming issues in the administration of poorly watersoluble medicines, gene therapy agents, and vaccines. Nanocochleates have shown promise in preclinical trials for the management of inflammatory diseases, cancer, and infectious diseases. Despite their potential, further research is needed to optimize large-scale manufacturing, maintain uniform quality, and address regulatory challenges. This review provides a detailed discussion of nanocochleate preparation methods, with a particular focus on entrapment, hydrogel approaches, and dialysis methods. The paper reviews characterization experiments, including particle size measurements, encapsulation effectiveness, surface morphology, and in vitro release tests. Furthermore, the article discusses the feasibility of industrial-scale formation with pure lipid feedstock.