title: Tissue distribution evaluation of stealth pH-sensitive liposomal cisplatin versus free cisplatin in Ehrlich tumor-bearing mice.
abstract: Multidrug resistance and drug toxicity represent major obstacles to cancer chemotherapy. Drug delivery systems, such as liposomes, offer improved chemical stability of encapsulated drugs, enhanced accumulation in tumors and decreased toxicity. The aim of this study was to evaluate the tissue distribution of stealth pH-sensitive liposomes containing cisplatin (SpHL-CDDP), compared with free cisplatin (CDDP), in solid Ehrlich tumor-bearing mice. After administering a 6 mg/kg single intravenous bolus injection of either free radiolabeled cisplatin or SpHL containing radiolabeled cisplatin, blood and tissues were analyzed for cisplatin content by determining radioactivity using an automatic scintillation apparatus. The area under the CDDP concentration-time curve (AUC) obtained for blood after SpHL-CDDP administration was 2.1 fold larger when compared with free CDDP treatment. The longer circulation of SpHL-CDDP led to a higher tumor AUC, and the determination of the ratio between AUC in each tissue and that in blood (Kp) showed a higher accumulation of CDDP in SpHL-CDDP administrated tumors. The SpHL-CDDP was also significantly uptaken by the liver and spleen. The distribution of SpHL-CDDP in these organs was extensive, revealing a high extravasation of CDDP to the tissues. The SpHL-CDDP kidney uptake was also greater than that of free CDDP; however, the Kp value found was lower. This indicates that the SpHL-CDDP led to a reduction of CDDP retention by renal tissue. Thus, these results indicate that the SpHL-CDDP may indeed be useful in alleviating renal damage induced by CDDP and thus represents a promising delivery system for cancer treatment through CDDP.
authors.affiliation: Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31279-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Alvaro D C
authors.initials: AD
authors.lastname: Júnior
authors.forename: Luciene G
authors.initials: LG
authors.lastname: Mota
authors.forename: Elzíria A
authors.initials: EA
authors.lastname: Nunan
authors.forename: Alberto J A
authors.initials: AJ
authors.lastname: Wainstein
authors.forename: Ana Paula D L
authors.initials: AP
authors.lastname: Wainstein
authors.forename: Alexandre S
authors.initials: AS
authors.lastname: Leal
authors.forename: Valbert N
authors.initials: VN
authors.lastname: Cardoso
authors.forename: Mônica C
authors.initials: MC
authors.lastname: De Oliveira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008081:Liposomes; D051379:Mice; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D002945:Cisplatin