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Ocular toxicity of intravitreally injected liposomal amphotericin B in rhesus monkeys
Abstract:
We determined whether liposome-intercalated amphotericin B was less toxic than commercial amphotericin B when injected intravitreally in the primate. Three rhesus monkeys were studied on each of three occasions. Each eye received increasing doses of amphotericin B (10, 20, or 30 micrograms) or liposome-intercalated amphotericin B (40, 80, or 120 micrograms) as a single intravitreal injection. There were often transient inflammatory changes in the anterior chamber and all eyes showed an acute cellular infiltrate in the vitreous humor after injection. These reactions had resolved by eight weeks after injection of the low or intermediate doses of amphotericin B (10 or 20 micrograms) or liposome-intercalated amphotericin B (40 or 80 micrograms) but left a mild vitreal infiltrate in the high-dose groups (30 micrograms of amphotericin B or 120 micrograms of liposome-intercalcated amphotericin B). Histologic examination at the end of the third experiment showed no abnormalities. These studies suggest that liposome incorporation reduces the toxicity of amphotericin B by at least fourfold and that as much as 30 micrograms of commercial amphotericin B may be tolerated by the intravitreal route in the rhesus monkey.
Insights
Liposome-intercalated amphotericin B shows reduced toxicity compared to commercial amphotericin B in primate intravitreal injections. This liposomal formulation may offer a safer alternative for ocular treatments.
Area of Science:
- Ophthalmology
- Pharmacology
- Toxicology
Background:
- Amphotericin B is a potent antifungal agent used to treat ocular infections.
- Intravitreal injections of amphotericin B can cause ocular toxicity.
- Liposomal formulations are designed to improve drug delivery and reduce toxicity.
Purpose of the Study:
- To compare the toxicity of liposome-intercalated amphotericin B with commercial amphotericin B following intravitreal injection in primates.
- To determine the maximum tolerated dose of both formulations via the intravitreal route.
Main Methods:
- Intravitreal injections of escalating doses of amphotericin B (10-30 µg) or liposome-intercalated amphotericin B (40-120 µg) were administered to rhesus monkey eyes.
- Ocular inflammatory responses and vitreous cellular infiltrates were monitored.
- Histopathological examination was performed at the study's conclusion.
Main Results:
- Transient anterior chamber inflammation and acute vitreous cellular infiltrates were observed in all groups.
- Reactions resolved by eight weeks for lower doses (10-20 µg amphotericin B; 40-80 µg liposomal amphotericin B).
- Mild persistent vitreal infiltrates occurred at high doses (30 µg amphotericin B; 120 µg liposomal amphotericin B); no histological abnormalities were noted.
Conclusions:
- Liposome incorporation significantly reduces amphotericin B toxicity by at least fourfold.
- Up to 30 µg of commercial amphotericin B may be tolerated intravitreally in rhesus monkeys.
- Liposomal amphotericin B presents a potentially safer option for intravitreal antifungal therapy.