Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin

0346588 - ÚMCH 2011 RIV GB eng J - Journal Article
Talelli, M. - Iman, M. - Varkouhi, A. K. - Rijcken, C. J. F. - Schiffelers, R. M. - Etrych, Tomáš - Ulbrich, Karel - van Nostrum, C. F. - Lammers, T. - Storm, G. - Hennink, W. E.
Core-crosslinked polymeric micelles with controlled release of covalently entrapped doxorubicin.
Biomaterials. Roč. 31, č. 30 (2010), s. 7797-7804. ISSN 0142-9612. E-ISSN 1878-5905
R&D Projects: GA AV ČR KAN200200651; GA AV ČR IAA400500806
Institutional research plan: CEZ:AV0Z40500505
Keywords : doxorubicin * cancer therapy * polymeric micelle
Subject RIV: CD - Macromolecular Chemistry
Impact factor: 7.883, year: 2010

A physically entrapped anticancer drug (paclitaxel) was previously shown to be rapidly eliminated from the circulation, likely because the drug was insufficiently retained in the micelles. To fully exploit the EPR effect for drug targeting, a DOX methacrylamide derivative (DOX-MA) was covalently incorporated into the micellar core by free radical polymerization. The structure of the doxorubicin derivative is susceptible to pH-sensitive hydrolysis, enabling controlled release of the drug in acidic conditions (in either the intratumoral environment and/or the endosomal vesicles). The entire drug payload was released within 24 h incubation at pH 5 and 37 °C, whereas only around 5% release was observed at pH 7.4. DOX micelles showed higher cytotoxicity in B16F10 and OVCAR-3 cells compared to DOX-MA, likely due to cellular uptake of the micelles via endocytosis and intracellular drug release in the acidic organelles.
Permanent Link: http://hdl.handle.net/11104/0005991