Abstract
AbstractWe have previously reported that the scavenger receptor-mediated uptake of para-aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) resulted in elimination of intracellular Mycobacterium tuberculosis (MTB) in mouse peritoneal macrophages in culture (Majumdar, S., and Basu, S. K. (1991) Antimicrob. Agents Chemother. 35, 135–140). In this paper, we report therapeutic efficacy of PASMBSA conjugate in vivo against MTB infection in guinea pigs. Two or 4 intravenous (iv) injections of PAS–MBSA conjugate weekly led to a greater reduction in the number of bacteria in the lung, liver, and spleen of the infected animals than the reduction caused by free PAS. PAS–MBSA treatment also in-creased the survival rate of the infected animals. High and persistent drug activity was observed in the target organs when the drug was delivered as PAS–MBSA conjugate. The superior efficacy of PAS–MBSA is presumably due to selective delivery of the conjugate to the macrophages, resulting in enhance...
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