In vivo distribution of arsenic after i.p. injection of arsonoliposomes in balb-c mice

• Published in: International journal of pharmaceutics 2005-01, Vol.289 (1), p.151-158
• Main Authors: Antimisiaris, Sophia G., Klepetsanis, Pavlos, Zachariou, Venetia, Giannopoulou, Eleftheria, Ioannou, Panagiotis V.
• Format: Article
• Language: English
• Subjects: Animals; Arsenate; Arsenic; Arsenicals - administration & dosage; Arsenicals - metabolism; Arsenicals - pharmacology; Biological and medical sciences; Distribution; Drug Evaluation, Preclinical - methods; Female; General pharmacology; In vivo; Injections, Intraperitoneal; Liposome; Liposomes; Medical sciences; Mice; Mice, Inbred BALB C; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Time Factors; Tissue; Tissue Distribution - drug effects; Toxicity
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2004.11.002

We recently showed that arsonoliposomes (novel arsenic containg liposomes) demonstrate differential toxicity towards various types of cancer and normal cells, in cell culture studies, as well as anti-parasitic activity. In this study, the in-vivo distribution of the active moiety of these vesicles, As, is evaluated. Sonicated arsonoliposomes were prepared using the arsonolipid with palmitic acid acyl chain (C16) mixed with egg-phosphatidyl choline (PC) and cholesterol (Chol) [C16/PC/Chol at 8:12:10 mol/mol/mol]. A dose of arsonoliposomes, corresponding to 5 mg arsenate/kg was administered by intraperitoneal injection in balb-c mice. At various time points post-injection the mice were sacrificed and the distribution of As in the organs was measured, by atomic absorption spectroscopy. Results demonstrate that a high portion of the dose administered is rapidly excreted; since 1-h post-injection only about 30% of the dose administered was detected cumulatively in the animal tissues. After this the elimination of arsenic was a slow process with a total body elimination rate constant of 0.023 h −1, corresponding to a half-life of 30 h. Tissues with the highest arsenic concentration during the study period are: spleen–kidneys–stomach, followed by lung, liver, intestines–heart, carcass + skin and finally blood. No acute toxicity, or effect on the body or organ weight of the mice was observed.