Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing ¹⁵⁹Gd-DTPA-BMA in Ehrlich tumor bearing mice

Daniel Crístian Ferreira Soares; Valbert Nascimento Cardoso; André Luís Branco de Barros; Cristina Maria de Souza; Geovanni Dantas Cassali; Mônica Cristina de Oliveira; Gilson Andrade Ramaldes

doi:10.1016/j.ejps.2011.10.018

Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing ¹⁵⁹Gd-DTPA-BMA in Ehrlich tumor bearing mice

Eur J Pharm Sci. 2012 Jan 23;45(1-2):58-64. doi: 10.1016/j.ejps.2011.10.018. Epub 2011 Nov 4.

Authors

Daniel Crístian Ferreira Soares¹, Valbert Nascimento Cardoso, André Luís Branco de Barros, Cristina Maria de Souza, Geovanni Dantas Cassali, Mônica Cristina de Oliveira, Gilson Andrade Ramaldes

Affiliation

¹ Universidade Federal de Minas Gerais - Avenida Presidente Antônio Carlos, 6627 - Pampulha - 31270-901 - Belo Horizonte, Minas Gerais, Brazil.

PMID: 22079137
DOI: 10.1016/j.ejps.2011.10.018

Abstract

In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the ¹⁵⁹Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage*
Antineoplastic Agents / adverse effects
Antineoplastic Agents / therapeutic use
Carcinoma, Ehrlich Tumor / pathology
Carcinoma, Ehrlich Tumor / radiotherapy*
Chemical and Drug Induced Liver Injury / pathology
Chemical and Drug Induced Liver Injury / physiopathology
Drug Delivery Systems* / adverse effects
Female
Folic Acid / analogs & derivatives*
Folic Acid / chemistry
Gadolinium
Gadolinium DTPA / administration & dosage*
Gadolinium DTPA / adverse effects
Gadolinium DTPA / therapeutic use
Hydrogen-Ion Concentration
Lethal Dose 50
Liposomes
Liver / pathology
Liver / physiopathology
Liver / radiation effects
Mice
Necrosis
Polyethylene Glycols / chemistry*
Radioisotopes
Radiopharmaceuticals / administration & dosage*
Radiopharmaceuticals / adverse effects
Radiopharmaceuticals / therapeutic use
Surface Properties
Tumor Burden / radiation effects
Weight Gain / radiation effects

Substances

Antineoplastic Agents
Liposomes
Radioisotopes
Radiopharmaceuticals
poly(ethylene glycol)-folate
Polyethylene Glycols
gadodiamide
Folic Acid
Gadolinium
Gadolinium DTPA