Abstract
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(e-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.
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