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Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif.


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.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC4229023 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif.

Zhang Xiaolan X   Huang Yixian Y   Zhao Wenchen W   Liu Hao H   Marquez Rebecca R   Lu Jianqin J   Zhang Peng P   Zhang Yifei Y   Li Jiang J   Gao Xiang X   Venkataramanan Raman R   Xu Liang L   Li Song S  

Biomacromolecules 20141028 11


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 sign  ...[more]

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