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壳聚糖-紫杉醇纳米粒-间充质干细胞给药系统的制备及释药机制。

Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system.

机构信息

Department of Pharmacy, Hebei University of Science and Technology, Yuhua East Road 70, Shijiazhuang 050018, PR China.

出版信息

Int J Pharm. 2013 Nov 1;456(1):186-94. doi: 10.1016/j.ijpharm.2013.07.070. Epub 2013 Aug 7.

DOI:10.1016/j.ijpharm.2013.07.070
PMID:23933442
Abstract

Targeting delivery of anticancer agents is a promising field in anticancer therapy. Inherent tumor-tropic and migratory properties of mesenchymal stem cells (MSCs) make them potential vehicles for targeting drug delivery systems for tumors. Although, MSCs have been successfully studied and discussed as a vehicle for cancer gene therapy, they have not yet been studied adequately as a potential vehicle for traditional chemical anticancer drugs. In this study, we have engineered MSCs as a potential targeting delivery vehicle for paclitaxel (TAX)-loaded nanoparticles (NPs). The size, surface charge, starving time of MSCs, incubating time and concentration of NPs could influence the efficiency of NPs uptake. In vitro release of TAX from CTS (chitosan)-TAX-NP-MSCs and the expression of P-glycoprotein demonstrated that release of TAX from MSCs might involve both passive diffusion and active transport. In vitro migration assays indicated that MSCs at passage number 3 have the highest migrating ability. Although, the migration ability of CTS-TAX-NP-MSCs could be inhibited by uptake of CTS-TAX-NPs, this ability could recover 6 days after the internalization.

摘要

靶向递药是癌症治疗中一个很有前景的领域。间充质干细胞(MSCs)固有的肿瘤趋向性和迁移特性,使它们成为靶向肿瘤药物递送系统的潜在载体。虽然 MSCs 已被成功研究并讨论作为癌症基因治疗的载体,但它们尚未被充分研究作为传统化学抗癌药物的潜在载体。在本研究中,我们构建了 MSCs 作为载紫杉醇(TAX)纳米颗粒(NPs)的靶向递药载体。MSCs 的大小、表面电荷、饥饿时间、孵育时间和 NPs 的浓度都会影响 NPs 的摄取效率。CTS(壳聚糖)-TAX-NP-MSCs 中 TAX 的体外释放和 P-糖蛋白的表达表明,MSCs 中 TAX 的释放可能涉及被动扩散和主动转运。体外迁移实验表明,第 3 代 MSCs 具有最高的迁移能力。尽管 CTS-TAX-NP-MSCs 的迁移能力可被 CTS-TAX-NPs 的摄取所抑制,但这种能力在摄取后 6 天可以恢复。

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