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)-a3,4 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.