HPMA copolymer-mitoxantrone conjugates for targeted cancer chemotherapy

The purpose of this study was to synthesize N-(2-hydroxypropyl) methacrylamide copolymer-mitoxantrone conjugates (HPMA-MTT), characterize their physicochemical properties, stability in vitro, biodistribution in vivo, selective tumor-accumulation and pharmacokinetics in mice hearing Ehrlich solid tumor Results demonstrate the conjugates were stable with low amounts of free MTT released (5% maximum) after incubation in phosphate buffers for 120 h at different pH (pH 2-8). The conjugates were also stable in mice plasma (< 10% drug released) over 72 h. The biodistribution of the coujugates in tumor-bearing mice was significantly different from that of the free drugs. The concentrations of HPMA-MTT in tumor reached maximum levels 24 h post-injection. A 3-fold larger area under the curve for HPMA-MTT was achieved when compared with that of free MTT. These results suggest the possibility of passively targeting anti. cancer drug-mitoxantrone, to the tumor tissue using HPMA copolymers as carrier.