Complex polymeric nanomicelles co-delivering doxorubicin and dimethoxycurcumin for cancer chemotherapy
Muhammad Sohail, Bin Yu, Zheng Sun, Jiali Liu, Yanli Li, Feng Zhao, Daquan Chen, Xin Yang, Hui Xu
Abstract
cytotoxicity assay, while the biocompatible diblock copolymer of mPEG2000-PLA5000 was selected for drug entrapment at an optimal feeding ratio of 9:1 to both drugs together. The uniform particles of CPM-DD with suitable particle size (∼30 nm) and stable drug loading content (>9%) could be reliably obtained by self-assembly with the encapsulation yield up to 95%. Molecular dynamics simulation revealed the interaction mechanism responsible for forming these complex nanomicelles. The acid-base interaction between two drugs would significantly improve their binding with the copolymer, thus leading to good colloidal stability and controlled drug release characteristics of CPM-DD. Systematic evaluation based on the MCF-7 breast tumor-bearing nude mice model further demonstrated the characteristics of tissue biodistribution of both drugs delivered by CPM-DD, which were closely related to the drug loading pattern and greatly responsible for the improved anti-cancer potency and attenuated toxicity of this complex formulation. Therefore, all the findings indicated that CPM-DD would be a good alternative to the conventional formulations of DOX and worthy of clinical application for cancer chemotherapy.