Renal-specific delivery of antifibrotic drugs using lysozyme: a novel approach for the treatment of renal fibrosis

The present thesis is focused on the development of a novel therapeutic system by which anti-fibrotic drugs can be delivered selectively to the kidneys. Renal fibrosis is a final common process of many chronic renal diseases. It is characterized by overdeposition of the extracellular matrix, which eventually leads to the end-stage renal disease (ESRD). Several renal disorders such as diabetic nephropathy, chronic glomerulonephritis, tubulointerstitial fibrosis and hypertensive nephrosclerosis can result into ESRD. The ultimate therapy for ESRD is dialysis or renal transplantation but these treatments have many medical and social disadvantages and are not always successful. The escalating prevalence of ESRD demands therefore for novel therapeutical strategies. Renal selective delivery aims to increase the therapeutic efficacy of drugs by increasing the amount of drugs locally within kidneys. The thesis attempts to provide a general overview of drug targeting approaches by encompassing different linking techniques to couple drug to LZM, different characterization techniques of drug-carrier conjugates, studies on in vitro drug-release and in vivo pharmacokinetic profiles of the conjugates. In addition, the pharmacological evaluation of the conjugates as described in the present study provides further insight in the role of the targeted kinases and profibrotic mediator systems, and thus may contribute to the development of novel therapies for renal fibrosis.