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Reduced toxicity of liposome-associated amphotericin B injected intravitreally in rabbits
Abstract:
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.
Insights
Liposomal amphotericin B significantly reduces ocular toxicity compared to commercial amphotericin B. This liposomal formulation shows improved safety for intravitreal injection in rabbits.
Area of Science:
- Ophthalmology
- Pharmacology
- Drug Delivery Systems
Background:
- Amphotericin B is a critical antifungal agent.
- Ocular toxicity is a concern with intravitreal amphotericin B injections.
- Liposomal formulations aim to improve drug safety and efficacy.
Purpose of the Study:
- To compare the ocular toxicity of liposomal amphotericin B (L-AMB) versus commercial amphotericin B (C-AMB).
- To evaluate the safety of intravitreal injections of these formulations in a rabbit model.
Main Methods:
- Intravitreal injections of L-AMB and C-AMB were administered to healthy pigmented rabbits.
- Ophthalmoscopic and histopathologic examinations were conducted over 5 weeks.
- Vitreous humor concentrations of amphotericin B were measured.
Main Results:
- Commercial amphotericin B caused retinal damage and vitreal bands at doses as low as 5 micrograms.
- Liposomal amphotericin B did not cause these lesions at doses up to 20 micrograms.
- Histopathology confirmed reduced retinal atrophy/necrosis with L-AMB (P = 0.02).
Conclusions:
- Liposome association markedly reduces the ocular toxicity of amphotericin B.
- Liposomal amphotericin B demonstrates a significantly improved ocular safety profile.
- This suggests L-AMB as a potentially safer alternative for intravitreal antifungal therapy.