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KMID : 0369820160460060575
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Jorunal of Korean Pharmaceutical Sciences
2016 Volume.46 No. 6 p.575 ~ p.582
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Preparation and in vivo evaluation of nanoliposomes containing melphalan after intravitreal injection in albino rabbits
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Naseripour Masood
Abrishami Majid
Sedaghat Ahad
Abrishami Mojtaba
Kanavi Mozhgan Rezaei
Mosallaei Navid
Falavarjani Khalil Ghasemi
Pourmatin Rama
Safarian Omid
Malaekeh Nikouei Bizhan
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Abstract
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The aim of present study was 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 and mean size of these liposomes and encapsulation efficacy of nanoliposomes 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 samples 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 protected melphalan completely from any undesirable release or hydrolysis for 48 h. In a histopathological study, signs of retinal toxicity were found in all doses in the liposomal group at least at one time point during the study. In melphalan injected eyes, histopathological 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. 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.
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KEYWORD
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Electrophysiology, Histopathology, Intravitreal injection, Melphalan, Nanoliposomes
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