Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapy
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Ferreira, Natália N. [UNESP]
M.B. Ferreira, Leonardo [UNESP]
Reis, Rui M.
Seraphim, Thiago V.
Borges, Júlio César
Gremião, Maria Palmira D. [UNESP]
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Anti-vascular endothelial growth factor (anti-VEGF) therapy applied to solid tumors is a promising strategy, yet, the challenge to deliver these agents at high drug concentrations together with the maintenance of therapeutic doses locally, at the tumor site, minimizes its benefits. To overcome these obstacles, we propose the development of a bevacizumab-loaded alginate hydrogel by electrostatic interactions to design a delivery system for controlled and anti-angiogenic therapy under tumor microenvironmental conditions. The tridimensional hydrogel structure produced provides drug stability and a system able to be introduced as a flowable solution, stablishing a depot after local administration. Biological performance by the chick embryo chorioallantoic membrane (CAM) assay indicated a pH-independent improved anti-angiogenic activity (∼50%) compared to commercial available anti-VEGF drug. Moreover, there was a considerable regression in tumor size when treated with this system. Immunohistochemistry highlighted a reduced number and disorganization of microscopic blood vessels resulting from applied therapy. These results suggest that the developed hydrogel is a promising approach to create an innovative delivery system that offers the possibility to treat different solid tumors by intratumoral administration.
Bevacizumab, Calcium alginate hydrogel, Protein delivery system, Supramolecular interactions, Tumor microenvironment
European Journal of Pharmaceutics and Biopharmaceutics, v. 119, p. 271-282.