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刚性段含量对阿托伐他汀作为扩链剂的嵌段聚氨酯性能的影响。

Effect of the rigid segment content on the properties of segmented polyurethanes conjugated with atorvastatin as chain extender.

机构信息

Centro de Investigación Científica de Yucatán, Calle 43 # 130×32y 34, Colonia Chuburná de Hidalgo, C.P. 97205, Mérida, Yucatán, Mexico.

Universidad Autónoma Metropolitana-Iztapalapa, CBI, Depto. de Física, Ave. San Rafael Atlixco, Colonia Vicentina, C.P. 09340, Cd. de México, Mexico.

出版信息

J Mater Sci Mater Med. 2018 Oct 24;29(11):161. doi: 10.1007/s10856-018-6165-y.

DOI:10.1007/s10856-018-6165-y
PMID:30357534
Abstract

Segmented polyurethanes were prepared with polycaprolactone diol as soft segment and various amounts of 4,4´-Methylenebis(cyclohexyl isocyanate) and atorvastatin, a statin used for lowering cholesterol, in order to obtain SPU with different content of rigid segments. Polyurethanes with 35% or 50% of rigid segment content were physicochemically characterized and their biocompatibility assessed with L929 fibroblasts. High concentrations of atorvastatin were incorporated by increasing the content of rigid segments as shown by FTIR, Raman, NMR, XPS and EDX. Thermal and mechanical characterization showed that polyurethanes containing atorvastatin and 35% of rigid segments were low modulus (13 MPa) semicrystalline polymers as they exhibited a glass transition temperature (T) at -38 °C, melting temperature (T) at 46 °C and crystallinity close to 35.9% as determined by DSC. In agreement with this, X-ray diffraction showed reflections at 21.3° and 23.6° for PCL without reflections for atorvastatin suggesting its presence in amorphous form with higher potential bioavailability. Low content of rigid segments led to highly degradable polymer in acidic, alkaline and oxidative media with an acceptable fibroblast cytotoxicity up to 7 days possibly due to low atorvastatin content.

摘要

将聚己内酯二醇作为软段,4,4'-亚甲基双(环己基异氰酸酯)和阿托伐他汀(一种用于降低胆固醇的他汀类药物)以不同的量制备了嵌段型聚氨酯,以获得具有不同刚性段含量的 SPU。对具有 35%或 50%刚性段含量的聚氨酯进行了物理化学特性表征,并通过 L929 成纤维细胞评估了其生物相容性。通过增加刚性段的含量可以掺入高浓度的阿托伐他汀,这可以通过 FTIR、Raman、NMR、XPS 和 EDX 来证明。热和机械特性表明,含有阿托伐他汀和 35%刚性段的聚氨酯是低模量(13 MPa)半结晶聚合物,因为它们在-38°C 处表现出玻璃化转变温度(Tg),在 46°C 处表现出熔融温度(Tm),并且结晶度接近 35.9%,这可以通过 DSC 来确定。与此一致的是,X 射线衍射在 21.3°和 23.6°处显示了 PCL 的反射,而阿托伐他汀没有反射,表明其以无定形形式存在,具有更高的潜在生物利用度。低刚性段含量导致聚合物在酸性、碱性和氧化介质中高度降解,在 7 天内具有可接受的成纤维细胞细胞毒性,这可能是由于阿托伐他汀含量低所致。

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PD-PK evaluation of freeze-dried atorvastatin calcium-loaded poly-ε-caprolactone nanoparticles.
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