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

How subtle differences in polymer molecular weight affect doxorubicin-loaded PLGA nanoparticles degradation and drug release
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DOI:
10.1080/02652048.2020.1729885
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发表时间:
2020-02-20
影响因子:
3.9
通讯作者:
Gelperina, Svetlana
Gelperina, Svetlana
中科院分区:
医学4区
文献类型:
--
作者:
Kumskova, Natalya;Ermolenko, Yulia;Gelperina, Svetlana

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目的:评价市售低相对分子质量PLGA的分子量微小差异对阿霉素纳米粒释放动力学的影响。方法:对三种低相对分子质量50/50的PLGA聚合物的特性粘度、相对分子质量、酸值和残留单体含量进行了详细的表征。对用这些聚合物制备的阿霉素纳米粒的药物释放和降解动力学进行了评价。结果:聚合物的相对分子质量略有不同,分别为10.2、10.3和4.7 kDa。由相对分子质量为4.7 kDa的聚合物得到的纳米粒子具有相当高的药物释放和聚合物降解速率。结论:在低分子量PLGA等级的情况下,甚至几千道尔顿对于纳米制剂参数的批间重复性可能是重要的。这些结果提出了用于纳米颗粒制备的聚合物的内部表征的重要性。
Aims: 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. Methods: 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. Results: 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. Conclusion: 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.