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聚合物分子量的细微差异如何影响载阿霉素 PLGA 纳米粒的降解和药物释放。

How subtle differences in polymer molecular weight affect doxorubicin-loaded PLGA nanoparticles degradation and drug release.

机构信息

D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia.

Drugs Technology LLC, Khimki, Russia.

出版信息

J Microencapsul. 2020 May;37(3):283-295. doi: 10.1080/02652048.2020.1729885. Epub 2020 Feb 20.

Abstract

To evaluate the influence of minor differences in molecular weights of commercially available low molecular weight PLGA grades on the kinetics of doxorubicin release from the nanoparticles. Three low-molecular weight 50/50 PLGA polymers were thoroughly characterised concerning intrinsic viscosity, molecular weight (Mw), acid value, and residual monomer content. The doxorubicin-loaded nanoparticles prepared using these polymers were evaluated concerning the kinetics of drug release and hydrolytic degradation. The Mw of the polymers were slightly different: 10.2, 10.3, and 4.7 kDa. The nanoparticles obtained from the polymer with Mw of 4.7 kDa exhibited considerably higher rates of drug release and polymer degradation. In the case of low molecular weight PLGA grades even a few kilodaltons could be important for the batch-to-batch reproducibility of the nanoformulation parameters. These results bring forward the importance of in-house characterisation of the polymers to be used for the nanoparticle preparation.

摘要

为了评估市售低分子量 PLGA 级分的分子量微小差异对纳米粒中阿霉素释放动力学的影响。我们对三种低分子量 50/50 PLGA 聚合物进行了全面的特性分析,包括特性黏度、分子量(Mw)、酸值和残留单体含量。使用这些聚合物制备载药纳米粒,并对其药物释放动力学和水解降解进行了评估。聚合物的 Mw 略有不同:10.2、10.3 和 4.7 kDa。Mw 为 4.7 kDa 的聚合物制备的纳米粒显示出明显更高的药物释放和聚合物降解速率。对于低分子量 PLGA 级分,即使相差几千道尔顿也可能对纳米制剂参数的批间重现性非常重要。这些结果强调了对用于纳米粒制备的聚合物进行内部特性分析的重要性。

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