Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration.
OBJECTIVE
The objective of this work was to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), after their intraperitoneal administration in male and female mice.


METHODS
After single administration of free CDDP (5,10,and 20 mg/kg) or SpHL-CDDP (7,12,30,45 and 80 mg/kg), the body weight was recorded and the LD(50) was calculated. Blood samples were collected for biochemical and hematological analysis. Kidneys, liver, spleen and bone marrow were removed to histopathological examination.


RESULTS
Mice treated with high doses of free CDDP showed a greater loss of body weight and more delayed recovery time than those treated with SpHL-CDDP. The LD(50) values for SpHL-CDDP treatment for male and female mice groups were 2.7 and 3.2 fold higher, respectively, than that obtained for free CDDP. The red and white blood cells counts and quantification of hemoglobin and hematocrit presented no change upon administration of SpHL-CDDP treatment. Free CDDP treatment, however, did lead to an appearance of mild anemia and a reduction in total white blood cell counts. As regards nephrotoxicity, it was observed that free CDDP treatment caused pronounced alterations in the blood urea and creatinine levels of mice. In contrast, these parameters were slightly altered only after SpHL-CDDP treatment at a dose of 30 mg/kg. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed no morphological alteration. Concerning hepatotoxicity, no histopathological alteration was observed after both treatments.


CONCLUSIONS
These findings reveal that SpHL-CDDP can eliminate CDDP-induced toxicity and is thus a promising candidate for intraperitoneal chemotherapy.
Leite
Elaine Amaral
EA
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil.
Giuberti
Cristiane dos Santos
Cdos S
Wainstein
Alberto J A
AJ
Wainstein
Ana Paula D L
AP
Coelho
Luiz G V
LG
Lana
Angela M Q
AM
Savassi-Rocha
Paulo R
PR
De Oliveira
Mônica Cristina
MC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D001853:Bone Marrow / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006403:Hematologic Tests; D006863:Hydrogen-Ion Concentration; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000166:cytology / Q000473:pathology; D008081:Liposomes / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D051379:Mice; D010534:Peritoneal Neoplasms / Q000188:drug therapy; D015996:Survival Rate
D000970:Antineoplastic Agents; D008081:Liposomes; D002945:Cisplatin