Doxorubicin and self-assembly: from main character to guest actor

The anticancer antibiotic doxorubicin (DX) is one of the most active drugs against both solid and systemic tumours. In water solutions, even at a 10-5M concentration, it is present for more than 50% as dimers. By rising the DX concentration to 10-2M and by adding a critical amount of NaCl, the solution turns into a thixotropic gel. Gel formation is due to the ability of doxorubicin to form, in the presence of salt, supramolecular helical chiral structures, similar to long fibers. One of the main concerns in the clinical use of DX is related to the severe side effects (cardiotoxicity being the principal) that impair its use. One strategy to overcome this problem is to host DX into suitable carriers (liposomes, mainly). Because of their self-assembly ability as well as to their intrinsically stealth nature, poly(ethylene oxide) (PEO)/poly(propylene oxide) (PPO) copolymers in general and F127 in particular, they can be used for DX vehiculation. To increase the solubility of DX in water, it is administered in the form of hydrochloride. Its cationic nature, however, limits its solubilization to the polar corona region of the F127 micelles. The cosolubilization with an anionic bile salt has been attempted to be used to drive the DX solubilization into the hydrophobic core of the F127 micelles. The NaC/F127 hydrophobic core provides a safe environment for DX, slowing down its degradation thus potentially increasing its latency time once injected into an organism. This should result into a reduction of the DX therapeutic dose thus leading to an attenuation of the undesired side-effects.