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

Abstract

Encapsulation of N-acetylmuramyl-L-.alpha.-aminobutyryl-D-isoglutamine in multilamellar vesicles composed of phosphatidylcholine, cholesterol and phosphatidylserine (7:6.7:3) or phosphatidylcholine and phosphatidylserine (7:3) reduced the amount of drug needed to protect [mice] against a C. albicans i.v. 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) i.v. Administration i.p., s.c. and orall was ineffective. Similar anti-Candida activity was observed whether the lower dose of drug was encapsulated in multilamellar vesicles, mixed with multilamellar vesicles or given 1 h before or 1 h after multilamellar vesicles. The mechanism of action probably involves retention of the liposomes by the RES, resulting in an enhanced macrophage response to the immunostimulating activity of the N-acetylmuramyl-L-.alpha.-aminobutyryl-D-isoglutamine given in conjuntion with the vesicles.