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Controlled release of paclitaxel from a self-assembling peptide hydrogel formed in situ and antitumor study in vitro

机译:从原位形成的自组装肽水凝胶和体外抗肿瘤研究中控制释放紫杉醇

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摘要

Background: A nanoscale injectable in situ-forming hydrogel drug delivery system was developed in this study. The system was based on a self-assembling peptide RADA16 solution, which can spontaneously form a hydrogel rapidly under physiological conditions. We used the RADA16 hydrogel for the controlled release of paclitaxel (PTX), a hydrophobic antitumor drug.Methods: The RADA16-PTX suspension was prepared simply by magnetic stirring, followed by atomic force microscopy, circular dichroism analysis, dynamic light scattering, rheological analysis, an in vitro release assay, and a cell viability test.Results: The results indicated that RADA16 and PTX can interact with each other and that the amphiphilic peptide was able to stabilize hydrophobic drugs in aqueous solution. The particle size of PTX was markedly decreased in the RADA16 solution compared with its size in water. The RADA16-PTX suspension could form a hydrogel in culture medium, and the elasticity of the hydrogel showed a positive correlation with peptide concentration. In vitro release measurements indicated that hydrogels with a higher peptide concentration had a longer half-release time. The RADA16-PTX hydrogel could effectively inhibit the growth of the breast cancer cell line, MDA-MB-435S, in vitro, and hydrogels with higher peptide concentrations were more effective at inhibiting tumor cell proliferation. The RADA16-PTX hydrogel was effective at controlling the release of PTX and inhibiting tumor cell growth in vitro.Conclusion: Self-assembling peptide hydrogels may work well as a system for drug delivery.
机译:背景:本研究开发了一种纳米级可注射原位形成的水凝胶药物递送系统。该系统基于自组装肽RADA16溶液,该溶液可在生理条件下快速自发形成水凝胶。我们将RADA16水凝胶用于疏水性抗肿瘤药物紫杉醇(PTX)的控释。方法:简单地通过磁力搅拌制备RADA16-PTX悬浮液,然后进行原子力显微镜,圆二色性分析,动态光散射,流变分析结果:结果表明,RADA16和PTX可以相互作用,并且两亲肽能够稳定水溶液中的疏水性药物。与在水中相比,在RADA16溶液中PTX的粒径明显减小。 RADA16-PTX悬浮液可以在培养基中形成水凝胶,并且水凝胶的弹性与肽浓度呈正相关。体外释放测量表明,具有较高肽浓度的水凝胶具有较长的半释放时间。 RADA16-PTX水凝胶可在体外有效抑制乳腺癌细胞系MDA-MB-435S的生长,肽浓度较高的水凝胶在抑制肿瘤细胞增殖方面更有效。 RADA16-PTX水凝胶可有效控制体外PTX的释放并抑制肿瘤细胞的生长。结论:自组装肽水凝胶可作为药物递送系统很好地发挥作用。

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