Dendrimer-like assemblies based on organoclays as multi-host system for sustained drug delivery.

Wei Li, Lili Sun, Lijun Pan, Zuopin Lan, Tao Jiang, Xiaolan Yang, Jianchun Luo, Ronghua Li, Liqing Tan, Shurong Zhang, Mingan Yu

Index: Eur. J. Pharm. Biopharm. 88(3) , 706-17, (2014)

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Abstract

Chemical modification of nanoclay will ensure further progress on these materials. In this work, we show that montmorillonite (MTM) nanosheets can be modified with β-cyclodextrin (CD) via a nucleophilic substitution reaction between mono-6-(p-toluenesulfonyl)-6-deoxy-β-CD and an amino group of 3-aminopropyltriethoxysilane (APTES)-functionalized MTM. The resulting MTM-APTES-CD can be further self-assembled into dendrimer-like assemblies, exhibit a well-dispersed property even in Dulbecco's phosphate-buffered saline and do not aggregate for a period of at least 20days. The structure, morphology and assembly mechanism are systematically studied by (29)Si MAS NMR, FT-IR, (1)H NMR, SEM, FE-TEM, DLS and AFM, and the change in assemblies during the drug release is monitored using FE-TEM images. MTT assays indicate that the assemblies only have low cytotoxicity, while CLSM and TEM observations reveal that the assemblies can easily penetrate cultured human endothelial cells. When clopidogrel is used as a guest molecule, the assemblies show not only much higher loading capacities compared to MTM and other containing β-CD assemblies or nanoparticles, but also a sustained release of clopidogrel up to 30days. This is attributed to the fact that the guest molecule is both supramolecularly complexed within the dendritic scaffold and intercalated into CD and MTM hosts. Host-guest systems between assemblies and various guests hold promising applications in drug delivery system and in the biomedical fields.Copyright © 2014 Elsevier B.V. All rights reserved.