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Development of Polymer Coacersome Structure with Enhanced Colloidal Stability for Therapeutic Protein Delivery.
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2019-10-28 , DOI: 10.1002/mabi.201900207
Heejung Jo 1 , Mani Gajendiran 2 , Kyobum Kim 2
Affiliation  

Poly(ethylene arginyl aspartate diglyceride) (PEAD) polycation is widely used to prepare coacervate particles by electrostatic complexation with an anionic heparin (HEP) in aqueous environments, for controlled release of therapeutic proteins. However, coacervate complexes aggregate randomly due to particle–particle charge interactions. Herein, a new term “coacersome” is introduced to represent a stable polyplex formed by complexation of mPEGylated PEAD and HEP. Methoxy polyethylene glycol (mPEG)‐b‐cationic PEAD diblock copolymers are synthesized and complexed with HEP to create a stable “coacersome” structure. Water‐soluble mPEG moiety assembles on the surface of coacersomes in aqueous conditions and creates a steric barrier to avoid aggregation of coacersomes. The coacersomes are able to maintain their initial spherical morphology and size for longer durations in the presence of competing ions, such as 0.3 m NaCl. Additionally, the coacersomes exhibit biocompatibility toward human dermal fibroblasts, a high loading efficiency (>96%) for encapsulation of bone morphogenetic protein 2 (BMP‐2), and a sustained release profile up to 28 days. The BMP‐2‐loaded coacersomes further exhibit increased osteogenic differentiation of human mesenchymal stem cells (hMSCs). The developed coacersome structures have the potential to be utilized as effective carriers for therapeutic protein delivery.

中文翻译:

具有增强的胶体稳定性的治疗蛋白传递的胶体稳定性聚合物的发展。

聚(精氨酸亚乙基天冬氨酸二甘油酯)(PEAD)聚阳离子广泛用于在水性环境中通过与阴离子肝素(HEP)进行静电络合来制备凝聚颗粒,以控制释放治疗性蛋白质。但是,凝聚粒子由于粒子间的电荷相互作用而随机聚集。在此,引入了新术语“ coacersome”,以表示通过mPEG化的PEAD和HEP的复合形成的稳定的复合物。甲氧基聚乙二醇(mPEG)-b合成阳离子PEAD二嵌段共聚物,并与HEP络合,形成稳定的“ coerersome”结构。水溶性mPEG部分在水性条件下会在coerersomes的表面组装,并形成空间屏障,以避免coerersome的聚集。在存在竞争离子(例如0.3 m)的情况下,coacersomes能够在更长的时间内保持其初始球形形态和大小。氯化钠 此外,coacersomes具有与人真皮成纤维细胞的生物相容性,骨形态发生蛋白2(BMP-2)封装的高负载效率(> 96%),以及长达28天的持续释放特性。载有BMP-2的coersomes进一步表现出人类间充质干细胞(hMSCs)的成骨分化增强。发达的coerersome结构具有潜力用作治疗性蛋白传递的有效载体。
更新日期:2019-10-28
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