Development and in Vitro Evaluation of Doxorubicin and Celecoxib Co-Loaded Bone Targeted Nanoparticles

Bone metastasis is one of the major problems for the treatment of cancer. Doxorubicin (DOX) is a potential drug for the treatment of bone metastasis with a limited usage due to systemic side effects. Also most of the many studies showed that celecoxib (CXB), a non-steroidal anti-inflammatory drug, have synergistic activity with DOX against cancer but usage of this combination is limited due to cytotoxicity of these drugs. In this study, it is aimed to reduce systemic side effects of these two synergic molecules (DOX and CXB) and increase efficacy of treatment. For this purpose, DOX and CXB co-loaded alendronate coated PLGA nanoparticles were prepared, optimized and fully characterized. Then, efficacy of nanoparticles was investigated by cytotoxicity, the calcium binding capacity and hydroxyapatite affinity tests. Results showed that fixed dose combination has been successfully generated and encapsulation ratio of DOX and CXB controlled by experimental design. Additionally cytotoxicity and targeting efficiency of the formulation has been clearly demonstrated. In conclusion, this study suggests that DOX and CXB co-loaded PLGA nanoparticles could be a promising approach for the treatment of bone metastases.