Validation of tumour models for use in anticancer nanomedicine evaluation: the EPR effect and cathepsin B-mediated drug release rate
| Autor: | Edward A. Sausville, Yee-Nee Sat-Klopsch, Ruth Duncan, Michael C. Bibby, Heinz H. Fiebig, Angelika M. Burger |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Polymers Vascular permeability Antineoplastic Agents Pharmacology Toxicology Cathepsin B Permeability chemistry.chemical_compound Mice In vivo Cell Line Tumor polycyclic compounds Animals Humans Nanotechnology Pharmacology (medical) Coloring Agents Leukemia L1210 Evans Blue Cathepsin Acrylamides Antibiotics Antineoplastic Drug release rate EPR effect Nanomedicines Xenograft Model Antitumor Assays Disease Models Animal chemistry Oncology Polyglutamic Acid Permeability (electromagnetism) HPMA copolymer–doxorubicin Doxorubicin Delayed-Action Preparations Nanomedicine Original Article |
| Zdroj: | Cancer Chemotherapy and Pharmacology |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | Purpose Intravenously (i.v.) administered nanomedicines have the potential for tumour targeting due to the enhanced permeability and retention (EPR) effect, but in vivo tumour models are rarely calibrated with respect to functional vascular permeability and/or mechanisms controlling intratumoural drug release. Here the effect of tumour type and tumour size on EPR-mediated tumour localisation and cathepsin B-mediated drug release was studied. Methods Evans Blue (10 mg/kg) and an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer–doxorubicin (Dox) conjugate (FCE28068) (5 mg/kg Dox-equiv) were used as probes and tumour levels (and Dox release) measured at 1 h after i.v. administration in a panel of murine and human xenograft tumours. Results Evans Blue and FCE28068 displayed similar tumour levels in the range of 2–18 % dose/g at 1 h for B16F10 and L1210. Approximately half of the tumour models evaluated exhibited tumour size-dependent accumulation of FCE28068; smaller tumours had the highest accumulation. Administration of free Dox (5 mg/kg) produced tumour levels of |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink