Hepatorenal effects of liposomal-encapsulated and free griseofulvin administration in rats

Abstract

Griseofulvin is an oral antifungal agent used for dermatophyte infections, but prolonged use may be associated with hepatic and renal adverse effects. This preclinical study compared the hepatorenal safety profile of free-form griseofulvin and liposome-encapsulated griseofulvin in male Sprague Dawley rats. Griseofulvin-loaded liposomes were prepared using the proliposome hydration method. Fifty-six rats were randomly allocated into two treatment arms: free-form griseofulvin and liposome-encapsulated griseofulvin. Each arm contained four dose subgroups (0, 1, 10, and 100 mg/kg; n = 7 biological replicates per subgroup), administered orally once daily for 14 days. Biochemical markers of renal and liver function (BUN, creatinine, AST, ALT, and ALP) were analyzed using an automated clinical chemistry analyzer, and liver and kidney tissues were evaluated histologically using hematoxylin and eosin staining. Free-form griseofulvin increased BUN at 10 and 100 mg/kg and increased creatinine, AST, and ALT at 100 mg/kg (p < 0.05). In contrast, liposome-encapsulated griseofulvin produced lower BUN and AST values than the equivalent free-drug doses and did not produce observable kidney lesions. Histology showed hepatic necrosis and renal congestion in free-drug groups, whereas liposome-encapsulated griseofulvin produced milder hepatic changes only at the highest dose. Because ALT values were not strictly dose-linear and liposome physicochemical characterization was not performed in the present experiment, the findings should be interpreted as preliminary safety evidence rather than definitive pharmacokinetic or efficacy proof.