A NEW BIOERODIBLE POLYMER INSERT FOR THE CONTROLLED-RELEASE OF METRONIDAZOLE
A NEW BIOERODIBLE POLYMER INSERT FOR THE CONTROLLED-RELEASE OF METRONIDAZOLE
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DOI：
10.1023/a:1018913921956
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发表时间：
1994-11-01
影响因子：
3.7
通讯作者：
LEE, PI
中科院分区：
文献类型：
--
作者：
GATES, KA;GRAD, H;LEE, PI
这项研究评估了一种新型生物可蚀性聚合物作为牙周插入物用于控制甲硝唑的释放。该系统基于由邻苯二甲酸醋酸纤维素 (CAP) 和聚氧乙烯和聚氧丙烯疏水性嵌段共聚物 Pluronic L101 的相容共混物形成的缔合聚合物。除了通过热分析表征这些聚合物之外，还使用大鼠模型在体外和体内测定了它们的侵蚀和甲硝唑释放特性。结果表明，将混合物中 Pluronic L101 的浓度提高到 50% 及以上会导致聚合物侵蚀和甲硝唑释放速率急剧降低。这些缓慢侵蚀薄膜的特性可能适合用作牙周药物插入物，有效持续时间长达数天。根据共混物的组成，发现甲硝唑释放的机制范围从表面侵蚀控制过程到侵蚀调节扩散过程。在所有体内实验中，没有检测到不良组织反应的迹象。根据这些结果，设计了原型递送插入物，并随后在志愿者患者中进行了评估。该初步研究的初步结果表明，龈沟液中甲硝唑的浓度在长达 3 小时的采样期内都很显着，并且远高于大多数牙周病原体的最低抑制浓度。此外，测试对象没有报告任何不适或刺激。
This study evaluates a new class of bioerodible polymers as periodontal inserts for the controlled release of metronidazole. The system is based on association polymers formed from compatible blends of cellulose acetate phthalate (CAP) and a hydrophobic block copolymer of polyoxyethylene and polyoxypropylene, Pluronic L101. In addition to characterizing these polymers by thermal analysis, their erosion and metronidazole release characteristics were determined both in vitro, and in vivo using a rat model. The results show that increasing the concentration of Pluronic L101 in the blend to 50% and above leads to a sharp reduction in the rates of polymer erosion and metronidazole release. The characteristics of these slowly eroding films are potentially suitable for use as periodontal drug inserts with an effective duration of up to several days. Depending on the blend composition, the mechanism of metronidazole release was found to range from a surface erosion-controlled process to an erosion-modulated diffusion process. In all in vivo experiments, no signs of adverse tissue reactions were detected. Based on these results, prototype delivery inserts were designed and subsequently evaluated in volunteer patients. Preliminary results from this pilot study show that the metronidazole concentration in the gingival crevicular fluid was significant throughout the sampling period of up to 3 hr and remained well above the minimum inhibitory concentration for most periodontal pathogens. In addition, no discomfort or irritation was reported by the test subjects.