Louka Dimitra A, Holwell Nathan, Thomas Brandon H, Chen Fei, Amsden Brian G
Department of Chemical Engineering, Queen's University, Kingston, Ontario K7L 3N6, Canada.
ACS Biomater Sci Eng. 2018 Nov 12;4(11):3747-3758. doi: 10.1021/acsbiomaterials.7b00403. Epub 2017 Oct 4.
Aliphatic polyester biodegradable microspheres have been extensively studied for controlled and minimally invasive in situ protein delivery. However, they are commonly characterized by protein denaturation via acidic polyester degradation products, whereas their supraphysiologic modulus contributes to the inflammatory response upon implantation. To address these limitations, low-melting-point poly(ε-caprolactone--glycolide)--poly(ethylene glycol)--poly(ε-caprolactone--glycolide) (PEG-(PCG)) copolymers were prepared and characterized for their ability to release bioactive stromal-derived factor-1α (SDF-1α) as a representative therapeutic protein. The PEG molecular weight was chosen such that it would be crystalline at room temperature to promote easy handling of the microspheres, whereas the molecular weight and composition of the hydrophobic PCG blocks were adjusted to ensure the polymer was a viscous amorphous liquid at 37 °C. Microspheres prepared from the triblock copolymers completely degraded within 8 weeks in vitro with a minor decrease in microenvironmental pH. A prolonged release of SDF-1α was observed with its bioactivity highly retained after encapsulation and release.
脂肪族聚酯可生物降解微球已被广泛研究用于可控且微创的原位蛋白质递送。然而，它们的共同特点是会因聚酯酸性降解产物导致蛋白质变性，而其超生理模量会在植入后引发炎症反应。为解决这些局限性，制备了低熔点聚（ε-己内酯-乙交酯）-聚（乙二醇）-聚（ε-己内酯-乙交酯）（PEG-(PCG)）共聚物，并对其释放生物活性基质衍生因子-1α（SDF-1α）作为代表性治疗性蛋白质的能力进行了表征。选择PEG分子量使其在室温下呈结晶态，以促进微球的易于处理，而疏水PCG嵌段的分子量和组成则进行了调整，以确保聚合物在37℃时为粘性无定形液体。由三嵌段共聚物制备的微球在体外8周内完全降解，微环境pH略有下降。观察到SDF-1α的持续释放，其生物活性在包封和释放后高度保留。
