Biodistribution and antitumoral effect of long-circulating and pH-sensitive liposomal cisplatin administered in Ehrlich tumor-bearing mice
| Autor: | Paulo Roberto Savassi-Rocha, Mônica Cristina de Oliveira, Márcio Tadeu Pereira, Laís de Carvalho Maroni, Valbert Nascimento Cardoso, Luciene das Graças Mota, José G. V. C. Araújo, Luiz Gonzaga Vaz Coelho, Alberto Julius Alves Wainstein, Andréa Teixeira de Carvalho, Elaine Amaral Leite |
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| Rok vydání: | 2011 |
| Předmět: |
inorganic chemicals
Biodistribution medicine.medical_treatment Antineoplastic Agents Pharmacology General Biochemistry Genetics and Molecular Biology Nephrotoxicity Peritoneal cavity Mice Pharmacokinetics medicine Animals Humans Carcinoma Ehrlich Tumor neoplasms Peritoneal Neoplasms Cisplatin Chemotherapy Drug Carriers business.industry Animal Structures Hydrogen-Ion Concentration Survival Analysis female genital diseases and pregnancy complications Disease Models Animal medicine.anatomical_structure Treatment Outcome Toxicity Drug delivery Liposomes business medicine.drug |
| Zdroj: | Experimental biology and medicine (Maywood, N.J.). 236(7) |
| ISSN: | 1535-3699 |
| Popis: | Cisplatin (CDDP) is one of the most active cytotoxic agents and has been widely used in the treatment of peritoneal carcinomatosis by the intraperitoneal (i.p.) route. However, CDDP, a low-molecular-weight compound, is rapidly absorbed by the capillaries in the i.p. serosa and transferred to the bloodstream, inducing the appearance of systemic side-effects, such as nephrotoxicity. Furthermore, the i.p. CDDP chemotherapy is limited to patients whose residual tumor nodules are less than 0.5 cm in diameter after surgical debulking. The failure of i.p. therapy is attributed to the poor penetration of CDDP into larger tumors. One strategy to improve drug delivery in the peritoneal region and reduce toxicity is the use of drug delivery systems. The objective of the present work was to evaluate the biodistribution and antitumoral effect of long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP), as compared with free CDDP, after their i.p. administration in Ehrlich ascitic tumor-bearing mice. After administering a 6 mg/kg single i.p. bolus injection of either free CDDP or SpHL-CDDP, ascitic fluid (AF), blood and organs (kidneys, liver, spleen and lungs) were collected and analyzed for CDDP content. The area under the CDDP concentration–time curve (AUC) obtained for AF and blood after SpHL-CDDP administration was 3.3-fold larger and 1.3-fold lower, respectively, when compared with free CDDP treatment, thus indicating its high retention within the peritoneal cavity. The determination of the ratio between AUC in each tissue and that in blood (Kp) showed a lower accumulation of CDDP in kidneys after SpHL-CDDP treatment. The SpHL-CDDP treatment demonstrated a significant uptake by the liver and spleen. SpHL-CDDP treatment led to a higher survival rate of mice with initial or disseminated peritoneal carcinomatosis than CDDP treatment. These results indicate that SpHL-CDDP may be useful for i.p. chemotherapy due to their greater concentration in the peritoneal cavity. |
| Databáze: | OpenAIRE |
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