Reduced toxicity of liposome-associated amphotericin B injected intravitreally in rabbits.
The ocular toxicity of liposome-intercalated amphotericin B and commercial amphotericin B were compared after intravitreal injection in healthy pigmented rabbits. Ophthalmoscopic observations over 5 weeks following a single intravitreal injection showed vitreal band formation and focal retinal damage after doses of commercial amphotericin B as low as 5 micrograms. Such lesions were not seen in animals given liposomal amphotericin B in doses up to 20 micrograms. Histopathologic examination showed areas of retinal atrophy or necrosis in five of 16 rabbits given commercial amphotericin B in doses of 5-20 micrograms but in none of 16 rabbits given the same doses of liposomal amphotericin B (P = 0.02). Small white vitreal bodies were seen clinically in virtually all animals given liposomal amphotericin B or "empty" (drug-free) liposomes but in only a few animals given commercial amphotericin B; these deposits may represent residual lipid. Concentrations of amphotericin B ranged from 0.4 to 1.0 micrograms per ml of vitreous humor 5 weeks after injection of 5-20 micrograms of either formulation. These studies indicate that liposome association markedly reduces the ocular toxicity of amphotericin B.
D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D007267:Injections; D008081:Liposomes; D011817:Rabbits; D012164:Retinal Diseases / Q000139:chemically induced* / Q000473:pathology; D014822:Vitreous Body / Q000187:drug effects* / Q000473:pathology
D008081:Liposomes; D000666:Amphotericin B