Renal Delivery of Captopril-Lysozyme

Angiotensin-converting enzyme (ACE) inhibitors such as captopril exert a long-term reno-protective effect. Among other effects, they lower systemic blood pressure and renal plasma flow and effectively reduce urinary protein excretion. Renal delivery of ACE-inhibitors may increase this efficacy and reduce extra-renal side-effects. Renal targeting of an ACE-in-hibitor can also be useful in clarifying the contribution of local ACE inhibition to these reno-protective effects. 

A spacer was used to link captopril via a disulfide bond to the LMWP lysozyme. Conjugation of captopril to lysoz5me resulted in a 6-fold increase in captopril accumulation in the rat kidney (Eigure 5.9b) [77]. This modest enrichment, as compared to that achieved with naproxen-lysozyme, was due to fact that, in contrast to naproxen, free captopril is cleared very efficiently by the kidney itself. Thus, delivery via lysozyme reabsorption only leads to a limited improvement of renal accumulation of captopril. 

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