To evaluate the stability and toxicity of different doses of liposomal melphalan in rabbit eyes and to investigate the pathological and electrophysiological changes after administration of different doses of free form of melphalan.

Liposomes containing melphalan were prepared by solvent evaporation method. The mean size of liposomes and encapsulation efficacy of drug were determined. In albino rabbits, intravitreal injections of 10, 20, and 40 µg doses of liposomal melphalan and Alkeran® as the commercial product was performed. The rabbits were euthanized at days 2, 7, 14, and 28, and the eyes were enucleated. Vitreous and aqueous sampling and electrophysiological recordings were obtained before euthanization. Histological examination was performed after enucleation.

Particle size of prepared liposomes was 143.6±3.2 nm. Liposomes have encapsulated melphalan completely (98.2%±3.2) and protected it completely from any undesirable release or hydrolysis for 48 hr. None of the melphalan or its metabolites were detected in vitreous and aqueous humor samples in days 14, 21, and 28 after intravitreal injection. In a histopathological study, signs of retinal toxicity were found in all doses in the liposomal group at least at one point in time during the study. In melphalan injected eyes, histological toxicity was found in the 40 µg dose. Extensive variability was found in electrophysiological recordings, and significant waveform changes were found in all injected eyes at least on one occasion during the study.

Intraocular administration of liposomal melphalan cannot prolong the drug clearance time of this drug in the vitreous humor, compared to commercial product. In the 40 µg injected eyes, significant retinal atrophic changes were detected in all eyes throughout the study, and electrophysiological results were consistent with histopathological findings.