Journal
JOURNAL OF CONTROLLED RELEASE
Volume 254, Issue -, Pages 23-33Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.03.391
Keywords
Paclitaxel; Dimer; Self-assembly; Nanomedicine
Funding
- National Natural Science Foundation of China [51522307, 51373167]
Ask authors/readers for more resources
Poor water solubility and adverse side effects pose a challenge for clinical application of paclitaxel (PTX). In this work, a series of PTX dimers are synthesized by coupling two PTX molecules with dicarboxylic acids. Assynthesized PTX dimers form stable nanoparticles in aqueous solution without using any surfactants or adjuvants, and the solubility of PTX in water increases by 2500-fold compared to that of free PTX. These nanoparticles with high content of PTX are internalized by cancer cells and exhibit comparable cytotoxicity with Taxol. Furthermore, when the PTX dimers are incorporated into methoxypoly(ethylene glycol)(2K)-block-poly(D, Llactide)(2K)(PEG-PDLLA) micelles, the loading content of PTX dimers is as high as 85 wt%. The formed nanoparticles possess the high stability in biological conditions. Both in vitro and in vivo experiments show that these (PTX dimer)/PEG-PDLLA formulations possess effective cellular uptake and potent cytotoxicity, and exhibit reduced systemic toxicity and enhanced antitumor efficacy towards human cervical tumor. We believe these PTX dimers-based nanoparticles would be an alternative formulation for PTX, and such drug dimer assembling behaviors could be extended to other therapeutic agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available