Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy

Publication date: Available online 21 April 2018 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Varun Kushwah, Sameer S. Katiyar, Ashish Kumar Agrawal, Ramesh C. Gupta, Sanyog Jain The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research