@article {19630, title = {Synergistic toxic effect of marine-origin polymeric nanoparticle loaded with gemcitabine over human breast cancer cells}, booktitle = {European Society for Biomaterials}, year = {2018}, month = {2018-09-11 00:00:00}, address = {Maastricht}, abstract = {

Introduction:Breast cancer is the most common cancer among women. To circumvent some drawbacks of current treatments, the use of natural polymers as biologically active compounds or in drug delivery devices may be a promising therapeutic alternative due to their similarities to native tissues. Fucoidan has been reported to present different biological activities, namely antitumor. However, from a previous study we observed that not all fucoidan extracts presented the desired antitumor behavior, which was related with different chemical features. In this work, a non-antitumor fucoidan extract was used to develop nanoparticles for the delivery of anticancer drugs.

Methods:\ Two marine origin polymers, fucoidan (negatively charged) and chitosan (positively charged), were chosen to produce nanoparticles by polyelectrolyte complexation.\ Gemcitabine, a hydrophilic drug commonly used to treat breast cancer, was encapsulated into the nanoparticles and the entrapment efficiency, release profile and the toxicity of the developed nanoparticles were evaluated over human endothelial and breast cancer cells.

Results and discussion:\ Nanoparticles final formulation presented a size around 115-140 nm and a polydispersity index \<0.2, demonstrating nanoparticles{\textquoteright} size homogeneity.\ Crosslinked and non-crosslinked nanoparticles\ were stable up to 2 months in storage conditions, whereascrosslinked nanoparticles were more stable at physiological conditions, as expected. Nanoparticles cytotoxic effect was evaluated over human breast cancer and endothelial cells, being only toxic for the highest concentrations tested. Gemcitabine was used as antitumor drug model and encapsulated at a maximum entrapment efficiency of 35-42\%.\ \ Drug release studies demonstrated that around 84\% of gemcitabine is released within 4h. Cytotoxicity results of gemcitabine-loaded nanoparticles showed increased toxicity (around 25\%) when compared with free gemcitabine, without increasing toxic effects over human endothelial cells.

Conclusion:\ The devolved drug delivery system was able to increase the toxic effects over human breast cancer cells without affecting endothelial cells viability. This system may be a promising and interesting approach to be further explored on the development of more effective breast cancer therapies.\ 

}, keywords = {anti-cancer, gemcitabine, marine nanoparticles}, author = {Oliveira, C. and Neves, N. M. and Reis, R. L. and Martins, A. and Tiago, S. H.} }