Mesh : Humans Blood-Brain Barrier / metabolism Biocompatible Materials / chemistry pharmacology Polymerization Endothelial Cells / drug effects metabolism Polymers / chemistry pharmacology Glycerol / chemistry Epoxy Compounds / chemistry Cell Line Permeability Propylene Glycols / chemistry Propanols / chemistry

来  源:   DOI:10.1021/acs.biomac.4c00210   PDF(Pubmed)

Abstract:
Polyglycidol or polyglycerol (PG), a polyether widely used in biomedical applications, has not been extensively studied in its branched cyclic form (bcPG), despite extensive research on hyperbranched PG (HPG). This study explores the biomedical promise of bcPG, particularly its ability to cross the blood-brain barrier (BBB). We evaluate in vitro biocompatibility, endothelial permeability, and formation of branched linear PG (blPG) as topological impurities in the presence of water. Small angle X-ray scattering in solution revealed a fractal dimension of approximately two for bcPG and the mixture bc+blPG, suggesting random branching. Comparisons of cytotoxicity and endothelial permeability between bcPG, bc+blPG, and HPG in a BBB model using hCMEC/D3 cells showed different biocompatibility profiles and higher endothelial permeability for HPG. bcPG showed a tendency to accumulate around cell nuclei, in contrast to the behavior of HPG. This study contributes to the understanding of the influence of polymer topology on biological behavior.
摘要:
聚缩水甘油或聚甘油(PG),一种广泛用于生物医学应用的聚醚,尚未广泛研究其支链环状形式(BCPG),尽管对超支化PG(HPG)进行了广泛的研究。这项研究探索了bcPG的生物医学前景,特别是其穿越血脑屏障(BBB)的能力。我们评估了体外生物相容性,内皮通透性,以及在水的存在下形成作为拓扑杂质的支化线性PG(blPG)。溶液中的小角度X射线散射显示,bcPG和bcblPG混合物的分形维数约为2,暗示随机分支。bcPG之间的细胞毒性和内皮通透性的比较,bc+blPG,和HPG在使用hCMEC/D3细胞的BBB模型中显示不同的生物相容性谱和对HPG的更高的内皮通透性。bcPG显示出在细胞核周围积聚的趋势,与HPG的行为相反。这项研究有助于理解聚合物拓扑结构对生物行为的影响。
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