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Bioresorbable hydrogels prepared by photo-initiated crosslinking of diacrylated PTMC-PEG-PTMC triblock copolymers as potential carrier of antitumor drugs
Saudi Pharmaceutical Journal ( IF 4.1 ) Pub Date : 2020-01-31 , DOI: 10.1016/j.jsps.2020.01.008
Yuandou Wang , Laishun Xi , Baogang Zhang , Qingzhen Zhu , Feng Su , Katarzyna Jelonek , Arkadiusz Orchel , Janusz Kasperczyk , Suming Li

PTMC-PEG-PTMC triblock copolymers were prepared by ring-opening polymerization of trimethylene carbonate (TMC) in the presence of dihydroxylated poly(ethylene glycol) (PEG) with Mn of 6000 and 10,000 as macro-initiator. The copolymers with different PTMC block Lengths and the two PEGs were end functionalized with acryloyl chloride. The resulting diacrylated PEG-PTMC-DA and PEG-DA were characterized by using NMR, GPC and DSC. The degree of substitution of end groups varied from 50.0 to 65.1%. Hydrogels were prepared by photo-crosslinking PEG-PTMC-DA and PEG-DA in aqueous solution using a water soluble photo-initiator under visible light irradiation. The effects of PTMC and PEG block lengths and degree of substitution on the swelling and weight loss of hydrogels were determined. Higher degree of substitution leads to higher crosslinking density, and thus to lower degree of swelling and weight loss. Similarly, higher PTMC block length also leads to lower degree of swelling and weight loss. Freeze dried hydrogels exhibit a highly porous structure with pore sizes from 20 to 100 µm.

The biocompatibility of hydrogels was evaluated by MTT assay, hemolysis test, and dynamic clotting time measurements. Results show that the various hydrogels present outstanding cyto- and hemo-compatibility. Doxorubicin was taken as a model drug to evaluate the potential of PEG-PTMC-DA and PEG-DA hydrogels as drug carrier. An initial burst release was observed in all cases, followed by slower release up to more than 90%. The release rate is strongly dependent on the degree of swelling. The higher the degree of swelling, the faster the release rate. Finally, the effect of drug loaded hydrogels on SKBR-3 tumor cells was evaluated in comparison with free drug. Similar cyto-toxicity was obtained for drug loaded hydrogels and free drug at comparable drug concentrations. Therefore, injectable PEG-PTMC-DA hydrogels with outstanding biocompatibility and drug release properties could be most promising as bioresorbable carrier of hydrophilic drugs.



中文翻译:

通过二丙烯酸化PTMC-PEG-PTMC三嵌段共聚物的光引发交联制备的可生物吸收的水凝胶,作为抗肿瘤药物的潜在载体

PTMC-PEG-PTMC三嵌段共聚物是通过在二甲基化聚乙二醇(PEG)(Mn为6000和10,000作为大分子引发剂)存在下碳酸亚丙酯(TMC)的开环聚合反应制备的。用丙烯酰氯将具有不同PTMC嵌段长度的共聚物和两种PEG末端官能化。通过使用NMR,GPC和DSC对所得的二丙烯酸酯化的PEG-PTMC-DA和PEG-DA进行表征。端基的取代度从50.0%到65.1%不等。通过在可见光照射下使用水溶性光引发剂在水溶液中使PEG-PTMC-DA和PEG-DA光交联来制备水凝胶。确定了PTMC和PEG嵌段的长度和取代度对水凝胶溶胀和失重的影响。较高的取代度导致较高的交联密度,因此降低了肿胀和体重减轻的程度。同样,较高的PTMC块长度也会导致较低的溶胀度和重量减轻。冷冻干燥的水凝胶显示出高度多孔的结构,孔径为20至100 µm。

通过MTT测定,溶血试验和动态凝血时间测量来评估水凝胶的生物相容性。结果表明,各种水凝胶具有出色的细胞和血液相容性。以阿霉素为模型药物,以评估PEG-PTMC-DA和PEG-DA水凝胶作为药物载体的潜力。在所有情况下均观察到最初的爆发释放,然后缓慢释放直至90%以上。释放速率在很大程度上取决于溶胀程度。溶胀度越高,释放速度越快。最后,与游离药物比较,评估了载药水凝胶对SKBR-3肿瘤细胞的作用。在可比较的药物浓度下,对于载有药物的水凝胶和游离药物获得了相似的细胞毒性。因此,

更新日期:2020-01-31
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