title: Effect of intratumoral injection on the biodistribution and the therapeutic potential of HPMA copolymer-based drug delivery systems.
abstract: 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.
authors.affiliation: Clinical Cooperation Unit Radiotherapeutic Oncology, Department of Innovative Cancer Diagnosis and Therapy, German Cancer Research Center, Heidelberg 69120, Germany. t.lammers@dkfz.de
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.forename: Peter
authors.initials: P
authors.lastname: Peschke
authors.forename: Rainer
authors.initials: R
authors.lastname: Kühnlein
authors.forename: Vladimir
authors.initials: V
authors.lastname: Subr
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Peter
authors.initials: P
authors.lastname: Huber
authors.forename: Wim
authors.initials: W
authors.lastname: Hennink
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
mesh_terms: 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
chemical_list: D000178:Acrylamides; D011108:Polymers; C482378:N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate; D004317:Doxorubicin