Sequential combination therapy of ovarian cancer with degradable N-(2-hydroxypropyl)methacrylamide copolymer paclitaxel and gemcitabine conjugates.

ABSTRACT: For rapid and effective clinical translation, polymer-based anticancer therapeutics need long circulating conjugates that produce a sustained concentration gradient between the vasculature and solid tumor. To this end, we designed second-generation backbone-degradable diblock N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carriers and evaluated sequential combination therapy of HPMA copolymer-paclitaxel and HPMA copolymer-gemcitabine conjugates against A2780 human ovarian carcinoma xenografts. First, extensive in vitro assessment of administration sequence impact on cell cycle, viability, apoptosis, migration, and invasion revealed that treatment with paclitaxel conjugate followed by gemcitabine conjugate was the most effective scheduling strategy. Second, in an in vivo comparison with

SUBMITTER: Zhang R 

PROVIDER: S-EPMC4143033 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature