Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems.
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 and 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 and the tumor-to-organ ratios of carriers improved substantially. In addition, compared to intravenously and intratumorally applied free doxorubicin and 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 and routes of administration.
Lammers
Twan
T
Clinical Cooperation Unit Radiotherapeutic Oncology, Department of Innovative Cancer Diagnosis and Therapy, German Cancer Research Center, Heidelberg 69120, Germany. t.lammers@dkfz.de
Peschke
Peter
P
Kühnlein
Rainer
R
Subr
Vladimir
V
Ulbrich
Karel
K
Huber
Peter
P
Hennink
Wim
W
Storm
Gert
G
D000178:Acrylamides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D008297:Male; D011108:Polymers; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D014018:Tissue Distribution
D000178:Acrylamides; D011108:Polymers; C482378:N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate; D004317:Doxorubicin