A ß-Cyclodextrin-Albumin Conjugate for Enhancing Therapeutic Efficacy of Cytotoxic Drugs.

ABSTRACT

Enhancing the selectivity of anticancer drugs currently used in the clinic is of great interest in order to propose more efficient chemotherapies with fewer side effects for patients. In this context, we developed a ß-cyclodextrin trimer that binds to circulating albumin to form the corresponding bioconjugate in the bloodstream. This latter can then entrap doxorubicin following its i.v. administration via the formation of a host-guest inclusion complex and deliver the drug in tumors. In this study, we demonstrate that the ß-cyclodextrin trimer improves the therapeutic efficacy of doxorubicin for the treatment of a subcutaneous murine Lewis lung carcinoma (LLC) implanted in C57BL/6 mice. This outcome is associated with an increased deposition of doxorubicin in malignant tissues when used in combination with the ß-cyclodextrin trimer compared to the administration of the drug alone.