Centre of Organic Chemistry "Costin D. Nenitzescu", Romanian Academy, 202B Spl. Independentei CP 35-108, 060023 Bucharest, Romania.
Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, B-9000 Ghent, Belgium.
Biomacromolecules. 2021 Dec 13;22(12):5020-5032. doi: 10.1021/acs.biomac.1c00994. Epub 2021 Nov 10.
Poly(2-isopropenyl-2-oxazoline) (PiPOx) is emerging as a promising, versatile polymer platform to design functional materials and particularly biomaterials that rely on the hydrophilic character of the 2-oxazoline side units. To be able to assess the applicability of PiPOx in a biomedical context, it is essential to understand its stability and degradation behavior in physiological conditions. In the present work, the hydrolytic stability of PiPOx was systematically investigated as a function of pH during incubation in various buffers. PiPOx was found to be stable in deionized water (pH 6.9), to have good stability in basic conditions (pH 8 and 9), to be satisfactorily stable in neutral conditions (pH 7.4), and to have moderate to low stability in acidic conditions (decreases drastically from pH 6 to pH 1.2). At pH 4, PiPOx formed a crosslinked network in a timeframe of hours, while at pH 1.2, PiPOx was transformed to a water-soluble poly(-(2-hydroxyethyl)methacrylamide) type of structure over the course of 2 weeks. stability assays were performed in phosphate-buffered saline (pH 7.4), simulated body fluid (SBF) (pH 7.4), simulated saliva (pH 6.4), simulated intestinal fluid (pH 6.8), and plasma (pH 7.4) revealing that PiPOx is stable in these SBFs up to 1 week of incubation. When incubated in simulated gastric fluid (pH 1.2), PiPOx exhibited a similar degradation behavior to that observed in the buffer at pH 1.2, rendering a water-soluble structure. The presented results on the stability of PiPOx will be important for future use of PiPOx for the development of drug-delivery systems and biomedical applications, such as hydrogels.
聚(2-异丙基-2-恶唑啉)(PiPOx)作为一种有前途的多功能聚合物平台,正在被开发用于设计功能材料,特别是依赖 2-恶唑啉侧基亲水性的生物材料。为了能够在生物医学背景下评估 PiPOx 的适用性,了解其在生理条件下的稳定性和降解行为至关重要。在本工作中,系统研究了 PiPOx 在不同缓冲液中孵育时随 pH 值变化的水解稳定性。研究发现,PiPOx 在去离子水中(pH6.9)稳定,在碱性条件(pH8 和 9)下稳定性良好,在中性条件(pH7.4)下稳定性令人满意,在酸性条件(pH6 至 1.2)下稳定性适中至较低。在 pH4 时,PiPOx 在数小时内形成交联网络,而在 pH1.2 时,PiPOx 在 2 周内转变为水溶性的聚(-(2-羟乙基)甲基丙烯酰胺)型结构。在磷酸盐缓冲盐水(pH7.4)、模拟体液(SBF)(pH7.4)、模拟唾液(pH6.4)、模拟肠液(pH6.8)和血浆(pH7.4)中进行的稳定性测定表明,PiPOx 在这些 SBF 中稳定,孵育 1 周。当在模拟胃液(pH1.2)中孵育时,PiPOx 表现出与在 pH1.2 缓冲液中观察到的相似降解行为,形成水溶性结构。本研究中关于 PiPOx 稳定性的结果对于未来使用 PiPOx 开发药物输送系统和生物医学应用(如水凝胶)非常重要。