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Construction of micelles based on biocompatible pseudo-graft polymers via beta-cyclodextrin/cholesterol interaction for protein delivery

机译:通过β-环糊精/胆固醇相互作用,基于生物相容性假接枝聚合物的胶束构建

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A novel pseudo-graft copolymer was developed for protein delivery, based on the self-assembly of (6-(2-aminoethyl)- amino-6-deoxy)-cyclodextrin (beta-CDen)-modified poly(aspartic acid) (PASP-CD) with cholesterol-modified poly(D,L-lactide) (PLA-Chol) by host-guest inclusion complexation. The chemical structures of polymers were confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. These components were then investigated for their ability to form nanoparticles and encapsulate protein. The diameter of micelles in water ranged from 70 to 200 nm as determined by dynamic light scattering, and the micelles were spherical in shape as observed by transmission electron microscopy. A model protein, bovine serum albumin (BSA), was encapsulated into the pseudo-graft copolymer micelles. The encapsulation efficiency (EE) and loading capacity (LC) of BSA in the micelles could be well tuned by adjusting the composition of the pseudo-graft copolymers. The micelles with a lower molar ratio of CD and cholesterol (hydrophilic/hydrophobic) exhibited a higher EE and LC. While in vitro release studies showed that a shorter chain of hydrophobic segment and higher hydrophilic/hydrophobic molar ratio could enhance the release rate. Cell viability studies showed that these materials possessed good cell viability (>95%). These results suggest that the degradable copolymers with appropriate hydrophilic and hydrophobic composition are able to self-assemble into micelles that are an effective and biocompatible vehicle for delivering protein, paving a new way for the application of pseudo-graft copolymers in protein or peptide delivery.
机译:基于(6-(2-氨基乙基)-氨基-6-脱氧)-环糊精(β-CDen)修饰的聚天冬氨酸(PASP)的自组装,开发了一种新型的假接枝共聚物用于蛋白质递送-CD)与胆固醇修饰的聚(D,L-丙交酯)(PLA-Chol)通过客体-客体包合络合。聚合物的化学结构通过傅里叶变换红外光谱和质子核磁共振光谱确认。然后研究这些组分形成纳米颗粒和包封蛋白质的能力。通过动态光散射测定,水中的胶束直径为70至200nm,并且通过透射电子显微镜观察,胶束的形状为球形。将模型蛋白牛血清白蛋白(BSA)封装到假接枝共聚物胶束中。通过调节假接枝共聚物的组成,可以很好地调节BSA在胶束中的包封效率(EE)和负载能力(LC)。 CD和胆固醇摩尔比(亲水/疏水性)较低的胶束具有较高的EE和LC。体外释放研究表明,较短的疏水链段和较高的亲水/疏水摩尔比可以提高释放速率。细胞活力研究表明,这些材料具有良好的细胞活力(> 95%)。这些结果表明,具有适当的亲水和疏水组成的可降解共聚物能够自组装成胶束,该胶束是一种有效的生物相容性蛋白传递载体,为假接枝共聚物在蛋白或肽传递中的应用开辟了新途径。

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