Treatment of lupus nephritis with nanoparticles that selectively target kidney glomeruli

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Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease. Lupus nephritis is the renal involvement in SLE with predominate glomerulus damage and exhibits a wide variety of symptoms from asymptomatic proteinuria to end-stage renal disease. Lupus nephritis requires aggressive immunosuppressive therapy, however, unfortunately most of these medications are associated with severe side effects. Therefore, development of new treatment strategies is essential. The goal of this proposal is to develop a nanoparticle delivery system that enables targeted drug delivery with stable and sustained release of prednisolone at the glomeruli as a novel therapeutic approach for lupus nephritis. Collagen IV (Col4)-α3,4 and 5 are expressed in the glomerular basement membrane (GBM), which is the only site in the body that Col4 has direct contact with blood via fenestrated capillary endothelium. Liposomes are one of the most widely used carriers due to their excellent biocompatibility and non-immunogenicity, but are lack of stability in terms of leakage of the encapsulated contents. Tripolyphosphate (TPP) cross-linked chitosan nanoparticles are characterized with controlled release of the loaded contents. Consequently, we hypothesize that by coupling Col4 binding peptides on the shell of liposomes filled with TPP-chitosan nanoparticles, we would make a kidney glomerulus selective delivery system with stable and sustained release of the loaded contents. We further hypothesize that this system loaded with prednisolone exhibits highly therapeutic efficiency due to the locally sustained drug release at a high concentration, meanwhile, it significantly minimizes the systemic side effects due to the very low dose of total prednisolone administered.