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用于依替膦酸递送的泊洛尼克和甲基纤维素的制备及其在成骨中的应用。

Fabrication of pluronic and methylcellulose for etidronate delivery and their application for osteogenesis.

作者信息

Rangabhatla Aparna Sai Laxmi, Tantishaiyakul Vimon, Oungbho Kwunchit, Boonrat Onpreeya

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai 90110, Thailand.

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai 90110, Thailand; PSU Center of Excellence for Drug Delivery System, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai 90110, Thailand.

出版信息

Int J Pharm. 2016 Feb 29;499(1-2):110-118. doi: 10.1016/j.ijpharm.2015.12.070. Epub 2015 Dec 31.

Abstract

Novel hydrogels were prepared by blending 4% (w/w) methylcellulose (MC) with various concentrations of 12, 14, 16, 18 and 20% (w/w) pluronic F127 (PF) to form injectable implant drug delivery systems. The blends formed gels using lower concentrations of PF compared to when using PF alone. Etidronate sodium (EDS) at a concentration of 4×10(-3)M was loaded into these blends for producing an osteogenesis effect. The pure gels or EDS loaded gels exhibited cytocompatibility to both the osteoblast (MC3T3-E1) and myoblast (C2C12) cell lines whereas the gels of 16PF, 18PF and 20PF were very cytotoxic to the cells. The EDS loaded gels demonstrated significantly greater alkaline phosphatase (ALP) activities compared to the pure gels. The longer exposure time periods of the samples to the cells, the greater was the ALP activity. These EDS loaded gels significantly increased proliferation of both cell lines thus indicating a bone regeneration effect. The PF/MC blends prolonged the in vitro release of EDS for more than 28 days. Based on the in vitro degradation test, the MC extensively improved the gel strength of the PF and delayed the degradation of the gels thus making them more functional for a sustained drug delivery for osteogenesis.

摘要

通过将4%(w/w)的甲基纤维素(MC)与12%、14%、16%、18%和20%(w/w)不同浓度的泊洛沙姆F127(PF)混合,制备了新型水凝胶,以形成可注射植入药物递送系统。与单独使用PF相比,这些混合物使用较低浓度的PF就能形成凝胶。将浓度为4×10(-3)M的依替膦酸钠(EDS)负载到这些混合物中以产生成骨作用。纯凝胶或负载EDS的凝胶对成骨细胞(MC3T3-E1)和成肌细胞(C2C12)细胞系均表现出细胞相容性,而16PF、18PF和20PF的凝胶对细胞具有很强的细胞毒性。与纯凝胶相比,负载EDS的凝胶表现出显著更高的碱性磷酸酶(ALP)活性。样品与细胞的接触时间越长,ALP活性越高。这些负载EDS的凝胶显著增加了两种细胞系的增殖,从而表明具有骨再生作用。PF/MC混合物使EDS的体外释放延长了28天以上。基于体外降解试验,MC显著提高了PF的凝胶强度并延迟了凝胶的降解,从而使其在成骨作用的持续药物递送方面更具功能性。

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