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水飞蓟宾聚乳酸-羟基乙酸共聚物纳米粒:一种用于前列腺癌治疗的有前景的候选药物。

Silymarin encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles: a prospective candidate for prostate cancer therapy.

出版信息

J Biomed Nanotechnol. 2014 Apr;10(4):559-70. doi: 10.1166/jbn.2014.1735.

Abstract

Silymarin, a clinically proved hepato-protective herbal drug having significant anti-cancerous property towards prostate cancer, is inadequately utilized for cancer therapy due to its hydrophobic nature and poor bioavailability. In this work, we have developed silymarin Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in order to improve the therapeutic efficacy of silymarin towards prostate cancer by single emulsion solvent evaporation technique. The prepared nanoparticles had an encapsulation efficiency of 60% and a loading efficiency of 13%. The silymarin-PLGA NPs (SNPs) characterization, using DLS and SEM analysis revealed its size as less than 300 nm. FT-IR analysis confirmed encapsulation of silymarin by the SNPs, whereas XRD and TGA proved amorphous nature of the SNPs. In vitro drug release study demonstrated a slow and sustained release of encapsulated drug from the SNPs in physiological conditions. The hemocompatibility of the SNPs was established by in vitro hemolysis and coagulation assays. In vitro cell viability studies revealed preferential toxicity of SNPs towards prostate cancer cells (PC-3) compared to normal cells (Vero) in a dose dependant way. Cell uptake studies using confocal microscopy confirmed internalization of the SNPs by PC-3 cells. Furthermore, in vitro cell migration assay showed a concentration and time dependent inhibitory effect of SNPs on PC-3 cell migration. Finally, flow-cytometry based apoptosis assay suggested induction of apoptosis mediated death in PC-3 cells by the SNPs. Overall, the prepared SNPs proved as a promising candidate for prostate cancer therapy.

摘要

水飞蓟素是一种经过临床验证的肝保护草药药物,具有显著的抗癌特性,可治疗前列腺癌,但由于其疏水性和生物利用度差,尚未充分用于癌症治疗。在这项工作中,我们使用单乳液溶剂蒸发技术开发了水飞蓟素聚(D,L-乳酸-共-乙醇酸)(PLGA)纳米粒(NPs),以提高水飞蓟素治疗前列腺癌的疗效。所制备的纳米粒具有 60%的包封效率和 13%的载药效率。使用 DLS 和 SEM 分析对水飞蓟素-PLGA NPs(SNPs)进行表征,结果表明其粒径小于 300nm。FT-IR 分析证实了 SNPs 对水飞蓟素的包封,而 XRD 和 TGA 则证明了 SNPs 的无定形性质。体外药物释放研究表明,在生理条件下,包封药物从 SNPs 中缓慢且持续释放。通过体外溶血和凝血测定确立了 SNPs 的血液相容性。体外细胞活力研究表明,与正常细胞(Vero)相比,SNPs 对前列腺癌细胞(PC-3)具有优先的毒性,且呈剂量依赖性。使用共聚焦显微镜进行的细胞摄取研究证实了 PC-3 细胞对 SNPs 的内化。此外,体外细胞迁移实验表明,SNPs 对 PC-3 细胞迁移具有浓度和时间依赖性的抑制作用。最后,基于流式细胞术的细胞凋亡实验表明,SNPs 诱导 PC-3 细胞发生凋亡介导的死亡。总的来说,所制备的 SNPs 有望成为治疗前列腺癌的候选药物。

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