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      Irinotecan and 5-fluorouracil-co-loaded, hyaluronic acid-modified layer-by-layer nanoparticles for targeted gastric carcinoma therapy

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          Abstract

          For targeted gastric carcinoma therapy, hyaluronic acid (HA)-modified layer-by-layer nanoparticles (NPs) are applied for improving anticancer treatment efficacy and reducing toxicity and side effects. The aim of this study was to develop HA-modified NPs for the co-loading of irinotecan (IRN) and 5-fluorouracil (5-FU). A novel polymer–chitosan (CH)–HA hybrid formulation (HA–CH–IRN/5-FU NPs) consisting of poly( d, l-lactide- co-glycolide) (PLGA) and IRN as the core, CH and 5-FU as a shell on the core and HA as the outmost layer was prepared. Its morphology, average size, zeta potential and drug encapsulation ability were evaluated. Human gastric carcinoma cells (MGC803 cells) and cancer-bearing mice were used for the testing of in vitro cytotoxicity and in vivo antitumor efficiency of NPs. HA–CH–IRN/5-FU NPs displayed enhanced antitumor activity in vitro and in vivo than non-modified NPs, single drug-loaded NPs and drugs solutions. The results demonstrate that HA–CH–IRN/5-FU NPs can achieve impressive antitumor activity and the novel targeted drug delivery system offers a promising strategy for the treatment of gastric cancer.

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          Most cited references 38

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          Analysis of combined drug effects: a new look at a very old problem

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            Layer-by-layer nanoparticles with a pH-sheddable layer for in vivo targeting of tumor hypoxia.

            Inspired by the simplicity and versatility of layer-by-layer (LbL) assembly, we applied multilayered polyelectrolyte assemblies on nanoparticles to create viable systemic delivery systems. Focusing on tumor-specific delivery, LbL nanoparticles that exhibit a pH-sensitive outer stealth layer are demonstrated to target and be retained in hypoxic tumor regions. The neutral layers shed in response to acidity to reveal a charged nanoparticle surface that is readily taken up by tumor cells. The first in vivo demonstration of this mechanism of targeting is presented, as well as an initial examination of the mechanism of uptake of the nanoparticles. We further demonstrate that this concept for tumor targeting is potentially valid for a broad range of cancers, with applicability for therapies that target hypoxic tumor tissue.
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              Factors Controlling the Growth of Polyelectrolyte Multilayers

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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                05 September 2017
                : 11
                : 2595-2604
                Affiliations
                [1 ]Department of General Surgery
                [2 ]Department of Pediatrics
                [3 ]Department of Renal Transplantation, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China
                Author notes
                Correspondence: Zhaoxia Li, Department of Pediatrics, The Second Hospital of Shandong University, No 247, BeiYuan Street, Jinan 250033, Shandong, People’s Republic of China, Email lizhaoxiasdu@ 123456sina.com
                Article
                dddt-11-2595
                10.2147/DDDT.S140797
                5592948
                © 2017 Gao et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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