Xiaolan Zhang, Yixian Huang, Wenchen Zhao
Oct 17, 2014
Citations
1
Influential Citations
24
Citations
Quality indicators
Journal
Biomacromolecules
Abstract
We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG5k–FTS2 led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG5k–Fmoc–FTS2 showed sustained release kinetics slower than those of DOX loaded in PEG5k–FTS2. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG5k–Fmoc–FTS2 was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG5k–Fmoc–FTS2 mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG5k–Fmoc–FTS2 led to superior antitumor activity over other treatments including drugs formulated in PEG5k–FTS2 in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents.