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

Paper ID Volume ID Publish Year Pages File Format Full-Text
6299 476 2013 15 PDF Available
Title
In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
Abstract

Nanoparticles 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.

Keywords
Chitosan nanoparticles; Methotrexate; Lysine-based surfactant; Intracellular drug delivery; pH-sensitivity; Cytotoxicity
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In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 11, April 2013, Pages 2758–2772
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us