Therapeutic efficacy-enhancing mechanisms:
- Direct targeting of APCs by PS-liposomes and presentation of T cell peptides.
- Effective uptake of liposomal T cell peptides by APCs.
- Effective tolerization of APCs by low oses of liposomal NF-kB inhibitors.
- Sustained delivery of tolerizing PS-liposomes for at least 3 days.
- Tolerance-supporting hydrogel technology (neither TH1- nor TH2-immune responses are triggered).
Subcutaneous injection of small amounts of tolerizing liposomes can avoid the risk of global tolerance via bystander suppression in various organs of the reticuloendothelial system. However, the uptake of tolerizing liposomes by phagocytes in subcutaneous tissues is not very effective. Therefore, this approach requires several repeated injections, a procedure that is not acceptable for physicians and patients.
Tolerogenic is solving these problems by utilizing hydrogel-embedded phosphatidylserine-presenting liposomes (PS-liposomes) loaded with allergen and the NF-κB inhibitors dexamethasone phosphate and/or vitamin D3 derivatives. Tolerizing PS-liposomes target antigen presenting cells since PS-liposomes mimic apoptotic cells and are phagocytosed mainly by macrophages and dendritic cells. As a result, the liposomal NF-κB inhibitors effectively generate tolerogenic DCs and, thereby, effectively induce tolerance promoting Tregs and minimizing side reactions. Furthermore, phagocytosis of PS-liposome-encapsulated allergen-derived peptides by DCs and macrophages guarantees effective presentation of the allergens and effective induction of tolerogenic Tregs.