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Fundamental insights in PLGA degradation from thin film studies.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2019-12-27 , DOI: 10.1016/j.jconrel.2019.12.044
Rainhard Machatschek 1 , Andreas Lendlein 2
Affiliation  

Poly(lactide-co-glycolide)s are commercially available degradable implant materials, which are typically selected based on specifications given by the manufacturer, one of which is their molecular weight. Here, we address the question whether variations in the chain length and their distribution affect the degradation behavior of Poly[(rac-lactide)-co-glycolide]s (PDLLGA). The hydrolysis was studied in ultrathin films at the air-water interface in order to rule out any morphological effects. We found that both for purely hydrolytic degradation as well as under enzymatic catalysis, the molecular weight has very little effect on the overall degradation kinetics of PDLLGAs. The quantitative analysis suggested a random scission mechanism. The monolayer experiments showed that an acidic micro-pH does not accelerate the degradation of PDLLGAs, in contrast to alkaline conditions. The degradation experiments were combined with interfacial rheology measurements, which showed a drastic decrease of the viscosity at little mass loss. The extrapolated molecular weight behaved similar to the viscosity, dropping to a value near to the solubility limit of PDLLGA oligomers before mass loss set in. This observation suggests a solubility controlled degradation of PDLLGA. Conclusively, the molecular weight affects the degradation of PDLLGA devices mostly in indirect ways, e.g. by determining their morphology and porosity during fabrication. Our study demonstrates the relevance of the presented Langmuir degradation method for the design of controlled release systems.

中文翻译:

薄膜研究对PLGA降解的基本见解。

聚(丙交酯-共-乙交酯)是可商购的可降解植入物材料,其通常根据制造商给出的规格进行选择,其中之一是它们的分子量。在这里,我们解决的问题是链长及其分布的变化是否会影响聚[(外消旋丙交酯)-共乙交酯](PDLLGA)的降解行为。为了排除任何形态学影响,在空气-水界面的超薄膜中研究了水解过程。我们发现对于纯水解降解以及在酶催化下,分子量对PDLLGA的整体降解动力学影响很小。定量分析提出了一种随机的分裂机制。单层实验表明,酸性微pH不会加速PDLLGA的降解,与碱性条件相反。降解实验与界面流变学测量相结合,显示出在质量损失很小的情况下粘度急剧下降。外推分子量的行为类似于粘度,在质量损失开始之前下降到接近PDLLGA低聚物的溶解度极限的值。该观察结果表明,PDLLGA的溶解度受控降解。最后,分子量主要以间接方式影响PDLLGA器件的降解,例如通过确定制造过程中其形态和孔隙率。我们的研究证明了所提出的Langmuir降解方法与控释系统设计的相关性。在几乎没有质量损失的情况下,粘度急剧降低。外推分子量的行为类似于粘度,在质量损失开始之前下降到接近PDLLGA低聚物的溶解度极限的值。该观察结果表明,PDLLGA的溶解度受控降解。最后,分子量主要以间接方式影响PDLLGA器件的降解,例如通过确定制造过程中其形态和孔隙率。我们的研究证明了所提出的Langmuir降解方法与控释系统设计的相关性。在几乎没有质量损失的情况下,粘度急剧降低。外推分子量的行为类似于粘度,在质量损失开始之前下降到接近PDLLGA低聚物的溶解度极限的值。该观察结果表明,PDLLGA的溶解度受控降解。最后,分子量主要以间接方式影响PDLLGA器件的降解,例如通过确定制造过程中其形态和孔隙率。我们的研究证明了所提出的Langmuir降解方法与控释系统设计的相关性。该观察结果表明PDLLGA的溶解度受控的降解。最后,分子量主要以间接方式影响PDLLGA器件的降解,例如通过确定制造过程中其形态和孔隙率。我们的研究证明了所提出的Langmuir降解方法与控释系统设计的相关性。该观察结果表明PDLLGA的溶解度受控的降解。最后,分子量主要以间接方式影响PDLLGA器件的降解,例如通过确定制造过程中其形态和孔隙率。我们的研究证明了所提出的Langmuir降解方法与控释系统设计的相关性。
更新日期:2019-12-27
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