Dimeric camptothecin-loaded mPEG-PCL nanoparticles with high drug loading and reduction-responsive drug release
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Camptothecin (CPT) is a potent and broad-spectrum anti-tumor drug, but its clinical application is limited due to its poor water solubility, toxicity, and low drug-loading potential. Different delivery protocols have been developed to optimize the therapeutic effects of CPT. In this study, CPT was modified into a dimer (CPT-Mal-CPT), in which two CPT molecules are connected by a reduction-responsive maleimide thioether bond. Moreover, biocompatible methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG–PCL)-loaded CPT-Mal-CPT nanoparticles were prepared to overcome the limits of CPT application. The power X-ray diffractometer (PXRD) results indicate low crystallinity and amorphous nature of CPT-Mal-CPT. The CPT-Mal-CPT-loaded micelles showed a drug-loading content of 9.6% and a drug-loading efficiency of 56%. In addition, dimeric CPT micelles showed reduction-responsive release under 10-mM dithiothreitol (DTT), while negligible CPT release was detected in the absence of DTT. MTT assay indicated that cytotoxicity of dimeric CPT micelle was similar to free CPT.
KeywordsmPEG-PCL Dimer Camptothecin Reduction-responsive Drug delivery
This work was supported by the Natural Science Project of the Education Department of Henan Province Natural Science Project(15A150053).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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