Effect of Intratumoral Injection on the Biodistribution, the Therapeutic Potential of HPMA Copolymer-Based Drug Delivery Systems 11

The direct intratumoral (i.t.) injection of anticancer agents has been evaluated extensively in the past few decades. Thus far, however, it has failed to become established as an alternative route of administration in routine clinical practice. In the present report, the impact of i.t. injection on the biodistribution, the therapeutic potential of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based drug delivery systems was investigated. It was found that, compared to intravenous injection, both the tumor concentrations, the tumor-to-organ ratios of carriers improved substantially. In addition, compared to intravenously, intratumorally applied free doxorubicin, to intravenously applied poly(HPMA)-glycylphenylalanylleucylglycine- doxorubicin, intratumorally injected poly(HPMA)-glycylphenylalanylleucylglycine-doxorubicin presented a significantly increased antitumor efficacy, as well as an improved therapeutic index. Based on these findings, we propose intratumorally injected carrier-based chemotherapy as an interesting alternative to routinely used chemotherapy regimens, routes of administration.