Anti-fibrotic Drugs

Several other agents are under study that are designed to produce combined blockade of COX and lipoxygenase. One such example is tenidap sodium, a novel antiarthritic agent, which also appears to block IL-1 formation and action [140]. 

Another drug that has been found to have anticytokine activity is pentoxifylline. It was initially characterized as a haemorheologic agent for the treatment of peripheral vascular diseases [141]. In addition, it was also found to be capable of inhibiting the pro-inflammatory actions of IL-1 and TNEa on neutrophil function and cytokine production by monocytic cells [142]. Its mechanism of action is the inhibition of phosphodiesterases, leading to increased intracellular levels of cyclic adenosine monophosphate [143]. Besides its effects on the cytokine network, pentoxifylline also exerted an anti-fibrogenic action in cultures of fibroblasts and in animal models of fibrosis [144] and could therefore be an attractive candidate for targeting hepatic inflammation. 

HSCs are the major contributors to the deposition of extracellular matrix in fibrotic livers and should therefore be the target for anti-fibrotic therapy. With the recent development of 

4 Cell Specific Delivery of Anti-Inflammatory Drugs to Hepatic Cells 

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Targeting of anti-inflammatory and anti-fibrotic drugs to the proximal tubular cell may prevent tubulointerstitial inflammation and scarring secondary to systemic and glomerular infection and proteinuria. Furthermore, tubular drug dehvery may be beneficial during shock, renal transplantation, ureter obstruction, diabetes, proteinuria, renal carcinoma and some tubular defect diseases such as Fanconi and Bartter s s5mdrome. 

L. Beljaars, G. Molema, B. Weert, H. Bonnema, P. Olinga, G. M. M. Groothuis, D. K. F. Meijer, and K. Poelstra, Albumin modified with mannose 6-phosphate a potential carrier for selective delivery of anti-fibrotic drugs to rat and human hepatic stellate cells, Hepatology 29 1486-1493 (1999). 

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