Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 119, Issue -, Pages 271-282Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2017.06.028
Keywords
Protein delivery system; Bevacizumab; Calcium alginate hydrogel; Tumor microenvironment; Supramolecular interactions
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Funding
- Brazilian Fundacao de Amparo e Pesquisa do Estado de Sao Paulo (FAPESP)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Northern Portugal Regional Operational Programme (NORTE) [NORTE-01-0145-FEDER-000013, PTDC/SAU-TOX/114549/2009 - FCOMP-01-0124-FEDER-016057]
- National funds, through the Foundation for Science and Technology (FCT) [POCI-01-0145-FEDER-007038]
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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 microenvironrnental 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 (similar to 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. (C) 2017 Elsevier B.V. All rights reserved.
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