Dimeric camptothecin-loaded mPEG-PCL nanoparticles with high drug loading and reduction-responsive drug release

• Published in: Colloid and polymer science Vol. 298; no. 1; pp. 51 - 58
• Main Authors: Chi, Yanwei, Wang, Zhiying, Wang, Jie, Dong, Wenpei, Xin, Pengyang, Bi, Jingjing, Jiang, Tao, Chen, Chang-Po
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2020; Springer Nature B.V
• Subjects: Biocompatibility; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Complex Fluids and Microfluidics; Dimers; Drug delivery systems; Food Science; Micelles; MPEG encoders; Nanoparticles; Nanotechnology and Microengineering; Original Contribution; Physical Chemistry; Polyethylene glycol; Polymer Sciences; Reduction; Soft and Granular Matter; Toxicity; Reduction-responsive; Camptothecin; Dimer; Drug delivery; mPEG-PCL
• ISSN: 0303-402X; 1435-1536
• DOI: 10.1007/s00396-019-04581-8

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.