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Development of conjugate-by-conjugate structured nanoparticles for oral delivery of docetaxel

Ha-Lien Tran, P., Wang, T., Yang, C., Tran, T.T.D. and Duan, W. (2020) Development of conjugate-by-conjugate structured nanoparticles for oral delivery of docetaxel. Materials Science and Engineering: C, 107 .

Link to Published Version: https://doi.org/10.1016/j.msec.2019.110346
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Abstract

In the current study, we developed interpolymer-complex structures composed of hydroxypropyl methylcellulose (HPMC) and chitosan knitted with d-α-tocopherol polyethylene glycol succinate (TPGS) to establish oral nanoparticle delivery systems that could keep the drug dose from releasing into the gastrointestinal tract for at least 6 h. Two kinds of nanoparticle formations based on the so-called conjugate-by-conjugate strategy were introduced in the study. In the first conjugate-by-conjugate structured nanoparticle formation, TPGS was conjugated with an HPMC-chitosan conjugate, followed by the drug loading process. In the second approach, the drug was loaded with TPGS directly and subsequently conjugated with the HPMC-chitosan conjugate. Beneficially, polyvinyl alcohol could act not only as a stabilizing agent but also as a crosslinking agent for the nanoparticles. This study created newly modified structures of HPMC and chitosan, altering their physicochemical properties that could then retard drug release. The nanoparticles were cytotoxic towards MDA-MB-231 breast cancer cells when docetaxel was loaded in the nanoparticles, particularly the nanoparticles produced in the second approach, demonstrating their ability to kill cancerous cells and their potential for further applications in cancer therapy. Additionally, when Caco-2 cells were used as an absorption model in a transport study, the nanoparticles in the second approach showed their capacity to increase drug permeability across the monolayers of Caco-2 cells compared to the free-drug solution. This study also illustrated the enhanced uptake of the nanoparticles by the Caco-2 cells, implying enhanced absorption through the intestine. Therefore, these oral nanoparticles can be considered for delivery systems of agents that are sensitive to the gastrointestinal tract so that they can be transported across the epithelial cells to the bloodstream to deliver the loading cargo at an optimal concentration.

Item Type: Journal Article
Murdoch Affiliation: Centre for Comparative Genomics
Publisher: Elsevier B.V.
Copyright: © 2019 Elsevier B.V.
URI: http://researchrepository.murdoch.edu.au/id/eprint/54115
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