Novel water-soluble polyurethane nanomicelles for cancer chemotherapy: physicochemical characterization and cellular activities

Journal of Nanobiotechnology

Research

Hossein Naderi-Manesh¹  Ahmad Yari Khosroushahi¹  Hamid Yeganeh²  Jaleh Barar³  Yadollah Omidi³ 

[1] Faculty of Bioscience, Tarbiat Modares University, Tehran, Iran;Faculty of Polymer Science, Iran Polymer and Petrochemical Institute (IPPI), Tehran, Iran;Research Centre for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran;Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, 19104, Philadelphia, PA, USA;

关键词: Bioactive biocompatible polymer;    Cancer chemotherapy;    Nanomicelle;    Nanoparticle;    Polyurethane;    Paclitaxel;   

DOI  :  10.1186/1477-3155-10-2

 received in 2011-09-07, accepted in 2012-01-05,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundEfficient delivery of anticancer chemotherapies such as paclitaxel (PTX) can improve treatment strategy in a variety of tumors such as breast and ovarian cancers. Accordingly, researches on polymeric nanomicelles continue to find suitable delivery systems. However, due to biocompatibility concerns, a few micellar nanoformulations have exquisitely been translated into clinical uses. Here, we report the synthesis of novel water-soluble nanomicelles using bioactive polyurethane (PU) polymer and efficient delivery of PTX in the human breast cancer MCF-7 cells.ResultsThe amphiphilic polyurethane was prepared through formation of urethane bounds between hydroxyl groups in poly (tetramethylene ether) glycol (PTMEG) and dimethylol propionic acid with isocyanate groups in toluene diisocyanate (TDI). The free isocyanate groups were blocked with phenol, while the free carboxyl groups of dimethylol propionic acid were reacted with triethylamine to attain ionic centers in the polymer backbone. These hydrophobic PTMEG blocks displayed self-assembly forming polymeric nanomicelles in water. The PTX loaded PU nanomicelles showed suitable physical stability, negative zeta potential charge (-43) and high loading efficiency (80%) with low level of critical micelle concentration (CMC). In vitro drug release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4, implying involvement of a pH-sensitive mechanism for drug release from the nanomicelles. The kinetic of release exquisitely obeyed the Higuchi model, confirming involvement of diffusion and somewhat erosion at pH 5.4. These nanomicelles significantly inhibited the growth and proliferation of the human breast cancer MCF-7 cells, leading them to apoptosis. The real time RT-PCR analysis confirmed the activation of apoptosis as result of liberation of cytochrome c in the cells treated with the PTX loaded PU nanomicelles. The comet assay analysis showed somewhat DNA fragmentation in the treated cells.ConclusionsBased upon these findings, we propose that the bioactive waterborne polyurethane nanomicelles can be used as an effective nanocarrier for delivery of anticancer chemotherapies such as paclitaxel.

【 授权许可】

Unknown   
© Khosroushahi et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.