Liposomal Delivery Systems for Allergen-Specific Immunotherapy: From Molecular Design to Clinical Application
Daria N. Melnikova, Andrey E. Potapov, Daria S. Zavoiko, Tatiana V. OvchinnikovaLiposomal systems are commonly used in drug delivery due to their low toxicity, biocompatibility and biodegradability. In this review, the influence of physicochemical parameters of liposomes, namely size, surface charge, and lipid composition, on biodistribution, dendritic cell uptake, and the character of the induced immune response is examined. The potential of strategies such as targeting C-type lectin receptors, the combined use of toll-like receptor agonists and tolerogenic molecules, and an approach based on high-affinity antigen binding to liposomes via coiled coil-forming peptides is evaluated. Mechanisms of tolerance induction at the humoral, cytokine, and cellular levels are discussed, including the switch from a Th2 to a regulatory T-cell response and the formation of blocking antibodies. Special attention is paid to safety aspects associated with the use of liposomal systems, specifically avoidance of pseudoallergic reactions linked to the complement system activation and the toxicity of cationic lipids, as well as approaches for minimization of these risks. The main obstacles to clinical application and promising directions of further research necessary for the development of effective and safe liposomal allergy vaccines are outlined. This review summarizes current data on the use of liposomal systems for allergen-specific immunotherapy.