A Novel Methotrexate Delivery System Based on Chitosan-Methotrexate Covalently Conjugated Nanoparticles
In this paper, a chitosan-methotrexate covalently conjugated nanoparticles (CS-MTX-TPP NPs) has been developed as a potential delivery system for methotrexate (MTX). MTX was first conjugated to CS by using glutaraldehyde as cross-linked agent, and followed by the process of ionic gelation between MTX-conjugated CS and sodium tripolyphosphate (TPP) to form CS-MTX-TPP NPs at mild reaction conditions. The hydrodynamic diameter of CS-MTX-TPP NPs and the encapsulation efficiency of MTX were affected by the weight ratio of MTX/CS. At the ratio of 1/11, the mean hydrodynamic diameter of CS-MTX-TPP NPs was the lowest (187.9±9.0 nm) and the nanoparticles presented the encapsulation efficiency of MTX with 53.0±3.2%. The characterizations by atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) showed the CS-MTX-TPP NPs had a spherical shape and good dispersion with diameter of sub-200-nm and zeta potential of 30 mV. Additionally, in vitro release test revealed that the stable covalent bonding of CS and MTX was beneficial for providing slow release for MTX. Especially, cellular toxicity study in MCF-7 cancer cells further demonstrated the effective anticancer efficacy of this new type of delivery for MTX.
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Document Type: Research Article
Publication date: October 1, 2009
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