Controlled release of core-shell ZSM-5/chitosan ellipsoids loaded with pifithrin-α for enhanced osteoinductivity

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): Rong Zhu, Yi-Xuan Chen, Qin-Fei Ke, Chang-Qing Zhang, Ya-Ping Guo
For enhanced osteoinductivity to treat effectively with bone defects, the design and fabrication of novel drug delivery systems remain a great challenge. Herein, we for the first time fabricated core-shell ZSM-5/chitosan ellipsoids loaded with pifithrin-α (ZSM-5/CS/PFTα ellipsoids). The ZSM-5 ellipsoids with long-axis lengths of ~400nm and short-axis lengths of ~300nm are constructed by many nanocrystals. The micropores and mesopores that exist respectively within and among the ZSM-5 nanocrystals serve as channels for loading PFTα. The CS on the ZSM-5/CS/PFTα ellipsoids increases drug loading efficiency up to 91.0%, and improves drug sustained release property. The ZSM-5/CS/PFTα ellipsoids possess excellent cytocompatibility, and promote the adhesion, spreading and proliferation of human bone mesenchymal stem cells (hBMSCs). Moreover, the released PFTα from the ZSM-5/CS/PFTα ellipsoids improves the ALP activity of hBMSCs, the mRNA relative expression levels of COL1, OCN and RUNX2, the ECM mineralization and the protein level of β-catenin. The reason is attributed to the fact that the released PFTα as a p53 inhibitor disrupts the ubiquitin-proteasome mediated degradation of β-catenin, resulting in the significant accumulation of β-catenin and the downstream transcription of genes involved in cell survival, proliferation and osteogenic differentiation.

Graphical abstract

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