Protective effect of a muramyl dipeptide analog encapsulated in or mixed with liposomes against Candida albicans infection

Abstract

Encapsulation of N-acetylmuramyl-L-α-aminobutyryl-D-isoglutamine in multilamellar vesciles composed of phosphatidylcholine, cholesterol, and phosphatidylserine (7:6.7:3) or phosphatidylcholine and phosphatidylserine (7:3) reduced the amount of drug needed to protect against a Candida albicans intravenous infection. The 50% effective doses for encapsulated and free drug were 5.5 and > 80 mg/kg, respectively. The optimum treatment was twice (at days 4 and 2 preinfection) by the intravenous route. Intraperitoneal, subcutaneous, and oral routes of administration were ineffective. The same potentiation of anti-Candida activity was observed whether the lower dose of drug was encapsulated in multilamellar vesicles, mixed with multilamellar vesicles, or given either 1 h before or 1 h after multilamellar vesicles. It was postulated that the mechanism of action involved the retention of the liposomes by organs of the reticuloendothelial system, resulting in an enhanced response of the macrophages to the immunostimulating activity of the N-acetylmuramyl-L-α-aminobutyryl-D-isoglutamine given in conjunction with the vesciles.