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In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

AutorNogueira, Daniele Rubert; Tavano, Lorena; Mitjans, Montserrat; Pérez, Lourdes F.; Infante, María Rosa; Vinardell, María Pilar
Palabras claveChitosan nanoparticles
Intracellular drug delivery
Lysine-based surfactant
Fecha de publicaciónabr-2013
ResumenNanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from Nα,Nε-dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CS-NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy. © 2013 Elsevier Ltd
Versión del editorhttp://dx.doi.org/10.1016/j.biomaterials.2013.01.005
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