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紫杉醇对由脂肪族聚酯和聚碳酸酯制成的基质中水解降解的影响。

The influence of paclitaxel on hydrolytic degradation in matrices obtained from aliphatic polyesters and polyester carbonates.

作者信息

Musiał-Kulik Monika, Kasperczyk Janusz, Jelonek Katarzyna, Dobrzyński Piotr, Gebarowska Katarzyna, Janeczek Henryk, Libera Marcin

机构信息

Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Zabrze 41-819, Poland.

出版信息

Acta Pol Pharm. 2010 Nov-Dec;67(6):664-8.

Abstract

Biodegradable polymers have become common materials used in pharmacy and medicine due to their properties such as mechanical strength, biocompatibility and non-toxic degradation products. Different compositions of copolymers and also their chain microstructure may have an effect on matrices degradation and thus on the drug release profile. In our study, we aimed at the influence of paclitaxel content on hydrolytic degradation process of terpolymeric matrices. Hydrolytic degradation of three kinds of matrices (with 5 or 10% of paclitaxel and drug free matrices) prepared from three types of terpolymers was performed in vitro at 37 degrees C in phosphate buffer solution (PBS, pH 7,4). The 1H and 13C NMR spectra of terpolymers were recorded. Thermal properties were monitored by differential scanning calorimetry (DSC). Molecular weight dispersity (D) and molecular weight were determined using gel permeation chromatography (GPC). The surface morphology was studied by means of the scanning electron microscopy (SEM). The most significant degradation was observed in case of poly(L-lactide-co-glycolide-co-epsilon-caprolactone) 44:32:24. Weight loss and water uptake were similar in the event of the same type of matrices obtained from the two poly(L-lactide-co-glycolide-co-TMC). Decelerated paclitaxel release in case of matrices with 51:26:23 molar ratio was noticed and it can be connected with higher content of carbonate units. Knowledge of paclitaxel influence on hydrolytic degradation process may contribute to receive valuable information about its release mechanisms from biodegradable terpolymers.

摘要

由于具有机械强度、生物相容性和无毒降解产物等特性,可生物降解聚合物已成为制药和医学领域常用的材料。共聚物的不同组成及其链微观结构可能会对基质降解产生影响,进而影响药物释放曲线。在我们的研究中,我们旨在研究紫杉醇含量对三元共聚物基质水解降解过程的影响。由三种类型的三元共聚物制备的三种基质(含5%或10%紫杉醇的基质以及不含药物的基质)在37℃下于磷酸盐缓冲溶液(PBS,pH 7.4)中进行体外水解降解。记录了三元共聚物的1H和13C NMR光谱。通过差示扫描量热法(DSC)监测热性能。使用凝胶渗透色谱法(GPC)测定分子量分散度(D)和分子量。通过扫描电子显微镜(SEM)研究表面形态。在聚(L-丙交酯-共-乙交酯-共-ε-己内酯)44:32:24的情况下观察到最显著的降解。由两种聚(L-丙交酯-共-乙交酯-共-三亚甲基碳酸酯)制得的相同类型基质的失重和吸水率相似。在摩尔比为51:26:23的基质中观察到紫杉醇释放减缓,这可能与较高的碳酸酯单元含量有关。了解紫杉醇对水解降解过程的影响可能有助于获得有关其从可生物降解三元共聚物中释放机制的有价值信息。

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