Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL), Spain.
Sagetis-Biotech, Spain.
Int J Pharm. 2019 Oct 5;569:118612. doi: 10.1016/j.ijpharm.2019.118612. Epub 2019 Aug 12.
Long-term stability of polyplexes used for biomedical purposes is an objective envisaged by any research group developing this kind of nanoformulations. However, since biodegradable polymers such as oligopeptide end-modified poly (β-aminoester) (OM-PBAE) are frequently used to ensure safety, and formulations are produced as aqueous dispersions, the stability of the nanoformulations is usually compromised. In this context, freeze-drying has aroused as a promising storage alternative to obtain solid nanoformulations with enhanced stability over time. Lyophilization is a challenging step that usually produces aggregation. Although some studies already achieved freeze-dried PBAE nanoparticles, none of them detailed the parameters that are critical for the success of this process. Moreover, due to the specific composition of each formulation, the critical parameters for the correct freeze-drying process need to be adjusted for each polyplex developed. In this paper, we have studied the variables that have a direct influence on the manufacturing and lyophilization of OM-PBAE nanoparticles with the aim to develop a versatile and robust freeze-drying receipt that properly preserves the library of polyplexes designed in our group, which have different pKa depending on the modification applied.
用于生物医学目的的聚合物复合物的长期稳定性是任何开发这种纳米制剂的研究小组的目标。然而，由于经常使用可生物降解的聚合物，如寡肽末端修饰的聚（β-氨基酯）（OM-PBAE）来确保安全性，并且制剂被制成水基分散体，因此纳米制剂的稳定性通常会受到影响。在这种情况下，冷冻干燥已成为一种有前途的储存替代方法，可以获得具有增强稳定性的固体纳米制剂。冷冻干燥是一个具有挑战性的步骤，通常会产生聚集。尽管已经有一些研究实现了冷冻干燥的 PBAE 纳米颗粒，但没有一个研究详细说明了该过程成功的关键参数。此外，由于每个制剂的特定组成，正确冷冻干燥过程的关键参数需要针对每个开发的聚合物复合物进行调整。在本文中，我们研究了直接影响 OM-PBAE 纳米颗粒制造和冷冻干燥的变量，目的是开发一种通用且强大的冷冻干燥方案，以正确保存我们小组设计的聚合物复合物库，这些复合物的 pKa 因所应用的修饰而不同。
