PolyMPC-Doxorubicin Prodrugs

Chen, X. J. and Parelkar, S. S. and Henchey, E. and Schneider, S. and Emrick, T.. (2012) PolyMPC-Doxorubicin Prodrugs. Bioconjugate Chemistry, 23 (9). pp. 1753-1763.

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We demonstrate the conjugation of the cancer drug doxorubicin (DOX) to poly(methacryloyloxyethyl phosphorylcholine) (polyMPC), linked by hydrazone groups, using (1) a one-pot ATRP/click sequence, and (2) a post-polymerization conjugation strategy. While the one-pot method gave polyMPC-DOX conjugates in a facile single step, post-polymerization conjugation gave higher-molecular-weight polymers with very high DOX loadings. DOX release from the polyMPC backbone was pH-dependent (faster at pH 5.0 than at pH 7.4) owing to the hydrazone linkage. Half-life values of DOX release ranged from 2 to 40 h at pH 5.0. Cell culture experiments showed that highly loaded polyMPC-DOX conjugates exhibited higher intracellular drug accumulation and lower half-maximal inhibitory concentration (IC50) values, while a polymer with 30 wt % drug loading showed a maximum tolerated dose in the range of 30-50 mg/kg DOX equivalent weight in healthy mice.

Item Type: Article
Additional Information: Chen, Xiangji Parelkar, Sangram S. Henchey, Elizabeth Schneider, Sallie Emrick, Todd
Collections: Nanomanufacturing Research Collection > Nanomanufacturing Nanoscale Science and Engineering Centers > Center for Hierarchical Manufacturing
Depositing User: Robert Stevens
Date Deposited: 26 Mar 2014
Last Modified: 26 Mar 2014 19:43
URI: http://eprints.internano.org/id/eprint/2035

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