Nano-rods of doxorubicin with poly(l-glutamic acid) as a carrier-free formulation for intratumoral cancer treatment†
In addition to intravenous injections (i.v.), topical dosing of doxorubicin hydrochloride (DOX) has also been the focus of cancer treatment recently, although it normally requires well-designed drug carriers. In this work, we found that DOX could form fibril-shaped DOX aggregates via self-assembly in phosphate buffer (PB) and then co-assemble with poly(L-glutamic acid) (PGA) at a proper polymer–drug ratio, giving a unique nano-rod-shaped microstructure. The release rate of DOX from the PGA/DOX nano-rods was thus easily controlled at a slower release rate without being encapsulated by any classic carrier. In vitro cell culture demonstrated that the PGA/DOX nano-rods were not favorably taken up by cancer cells, which can be attributed to the negatively charged nature and the non-spherical shape of the aggregates. These features suggest great potential for the PGA/DOX assemblies for a sustained delivery through the intratumoral pathway (i.t.) as a carrier-free formulation. In the mouse model it diminished organ damage at a dose level of 30 mg kg−1via i.t. injections compared to the serious cardiotoxicity and renal toxicity via typical multiple i.v. dosage of free drug solution at 5 mg kg−1. As a result, the PGA/DOX formulation showed efficient anti-tumor activity. The survival rate of tumor bearing mice was significantly increased by over 35% compared to the i.v. injections of DOX solutions. Therefore, PGA/DOX nano-rods may provide a new and safe delivery route of the common anti-tumor drug.