Preparation, Characterization and in Vitro Validation of a Novel Paclitaxel Transport System to Target HER2-Positive Breast Cancer

Breast cancer is the second kind of cancer with the highest frequency worldwide, and the leading cause of oncological death among women in both, developed and developing countries [1]. Among the different clinical subtypes, the HER2-positive one, associated with a worse prognosis for patients, represents the 15-30% of all of the breast tumor cases [2].

One of the most efficient drugs used in the management of this subtype of cancer is paclitaxel, a natural terpenoid compound [3]. However, it has a poor aqueous solubility and an elevated toxicity, and these facts limit its clinical application.

With the aim of sorting out both disadvantages, a novel transport system for paclitaxel has been designed: polymeric nanoparticles of sodium alginate and piperazine, developed thanks to the electrostatic interactions that take place between both compounds at slightly acid pH values [4].

In such transport system, paclitaxel has been included in β-cyclodextrins in order to improve its aqueous solubility and in addition, trastuzumab, an antibody that binds specifically to the HER2 receptor, has been attached for avoiding the severe side effects that the terpenoid drug has. Both, the paclitaxel-β-cyclodextrins complexes and the antibody, have been attached to nanoparticles’ surface by a diimide-activate amidation process, and the conjugation efficiency of both of them to the nanoparticles has been analyzed. Later, the characterization of the transport system has been carried out by determining the average size and zeta potential of the nanoparticles, their stability over time under different conditions and the paclitaxel release kinetics. Finally, the effectiveness of this novel paclitaxel transport vehicle has been validated in vitro, by MTT assays performed with the BT474 cell line, with which positive results have been obtained. In this manner, a new door could be opened to improve the specific treatment of the HER2 positive breast cancer.

References

[1] Amaro, J., Severo, M., Vilela, S., Fonseca, S., Fontes, F., La Vecchia, C. et al. 2013. Patterns of breast cancer mortality trends in Europe. The Breast 22, 244-253.

[2] Figueroa-Magalhaes, M.C., Jelovac, D., Connolly, R.M., Wolff, A.C. 2014. Treatment of HER2-positive breast cancer. The Breast 235, 128-136.

[3] Singla, A.K., Garg, A., Agarwal, D. 2002. Paclitaxel and its formulations. Int. J. Pharm. 235, 179-192.

[4] Román, J.V., Rodríguez-Rodríguez, J.A., Martín del Valle, E.M., Galán, M.A. 2016. Synthesis of a new nanoparticle system based on electrostatic alginate-piperazine interactions. Polymer Adv. Tech. 27(5), 623-629.