Biodegradable PLGA implants containing doxorubicin-loaded chitosan nanoparticles for treatment of breast tumor-bearing mice

Abstract

Drug-loaded implants have exhibited many advantages over intravenous or oral drug administration, especially for cancer treatment. Therefore, biodegradable implants have received lots of attention for controlled release and delivery of anti-cancer drugs. In the present study, doxorubicin-loaded chitosan (CS-DOX) nanoparticles were synthesized and characterized. Subsequently, polylactic-co-glycolic acid (PLGA) was used as a maintainer to form a biodegradable implant containing CS-DOX nanoparticles for subcutaneous implantation (PLGA/CS-DOX). The therapeutic efficacy of these implants was investigated in different groups of 4T1 breast tumor-bearing BALB/c mice including no-treatment, PLGA, PLGA/CS, PLGA/CS-DOX, and doxorubicin (5mg/kg/day). The most therapeutic efficacy was observed at PLGA/CS-DOX implants which significantly (P<0.05) inhibited breast tumors' growth and metastasis. The PLGA/CS-DOX implant was completely biodegradable and caused 71 and 62 decrease in the tumors' volume and lung metastatic nodules in comparison with no-treatment, respectively. In addition, 41days increase in the tumor-bearing mice survival of the PLGA/CS-DOX group was observed in comparison with the no-treatment group. Therefore, the subcutaneous implantation of PLGA/CS-DOX can be an appropriate choice for replacement of multiple-doses injections of doxorubicin for breast cancer treatment.