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聚(γ-谷氨酸)两亲性复合物作为一种新型药物传递系统的纳米载体。

A poly(gamma-glutamic acid)-amphiphile complex as a novel nanovehicle for drug delivery system.

机构信息

Biotechnology and Food Research Institute, Fukuoka Industrial Technology Center, Fukuoka, Japan.

出版信息

J Drug Target. 2010 Aug;18(7):550-6. doi: 10.3109/10611861003599453.

Abstract

Recently, many studies have focused on biomedical and pharmaceutical applications of self-assembled nanoparticles. In addition, several biodegradable nanoparticles have been reported to possess poor dispersion stability and poor size-controllability. However, these nanoparticles require complicated fabrication procedures using synthesis techniques. We developed an efficient method for producing nanoparticles derived from a biological origin of molecule poly(gamma-glutamic acid) (gamma-PGA), a cationic lipid, and doxorubicin (Dox). The complex had a size of 510 nm and was able to encapsulate over 90% of the added Dox. An in vivo assay of antitumor activity demonstrated that the complex had significant antitumor activity in sarcoma 180-bearing mice, and was effectively accumulated in solid tumors based on the EPR effect. The data suggested that this complex is a promising formulation of gamma-PGA for targeted delivery to solid tumors. gamma-PGA-12GP2 complexes may possess several unique advantages, including simplicity of nanoparticle preparation, high drug-carrying capacity, appropriate size to allow deeper penetration based on EPR effect into solid tumors, and lack of necessity to modify the chemical structure of the drugs. These data indicate that the gamma-PGA-12GP2 complexes are potentially useful in cancer chemotherapy.

摘要

最近,许多研究都集中在自组装纳米粒子在生物医学和药物方面的应用。此外,据报道,一些可生物降解的纳米粒子具有较差的分散稳定性和较差的尺寸可控性。然而,这些纳米粒子需要使用合成技术进行复杂的制造程序。我们开发了一种从生物来源的分子聚(γ-谷氨酸)(γ-PGA)、阳离子脂质和阿霉素(Dox)生产纳米粒子的有效方法。该复合物的尺寸为 510nm,能够包裹超过 90%的添加的 Dox。体内抗肿瘤活性试验表明,该复合物在荷肉瘤 180 小鼠中具有显著的抗肿瘤活性,并基于 EPR 效应有效地在实体瘤中积累。数据表明,该复合物是一种有前途的 γ-PGA 制剂,可用于靶向递送至实体瘤。γ-PGA-12GP2 复合物可能具有几个独特的优势,包括纳米粒子制备的简单性、高载药量、适当的尺寸,以允许基于 EPR 效应更深地渗透到实体瘤中,并且不需要修饰药物的化学结构。这些数据表明,γ-PGA-12GP2 复合物在癌症化疗中具有潜在的用途。

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