Sterilization of gentamicin containing collagen/PLGA microparticle composites
Sterilization of gentamicin containing collagen/PLGA microparticle composites
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DOI：
10.1016/j.ejpb.2005.11.007
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发表时间：
2006-06-01
影响因子：
4.9
通讯作者：
Schlapp, Monika
中科院分区：
文献类型：
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作者：
Friess, Wolfgang;Schlapp, Monika
为了获得提供庆大霉素持续释放的植入物，将基于50/50 Resomer（R）503/Resomer（R）502 H共混物的微粒与胶原结合，以实现它们的固定并利用胶原对伤口愈合的有利作用。测试环氧乙烷处理以及β-和γ-辐照对胶原/PLGA-微粒复合物的灭菌。所有方法均导致聚合物原料和微粒的分子量和玻璃化转变温度降低。此外，环氧乙烷处理产生微粒聚集，导致最初释放的庆大霉素剂量大幅增加。此外，庆大霉素的化学变化后，环氧乙烷灭菌可以确定使用NMR光谱。尽管辐照后分子量和玻璃化转变温度降低，但未观察到复合材料的形态变化，也未观察到β-和γ-灭菌材料中庆大霉素释放曲线的变化。仅在庆大霉素原料药中检测到自由基，在庆大霉素负载的MP中检测到边缘水平的自由基，在4周内消失。额外的微生物学试验验证了从P-灭菌复合材料中释放的庆大霉素的微生物活性。P-灭菌复合材料在4 ℃/35% r.h.下的储存持续3个月不影响微粒和复合物的形态、分子量、玻璃化转变温度和释放曲线。然而，在25摄氏度/60% r.h.和40 ℃/75% r.h.导致分子量和玻璃化转变温度显著降低。这种效应是由于较高的湿度、聚合物吸水以及随后聚合物和微粒的水解，由于RG 502 H的亲水性，这一点更为明显。储存于25 ℃/60% r.h.和40 ℃/75% r.h.颗粒塌陷导致庆大霉素释放增加。因此，所有灭菌技术都有其优缺点，但基于药物释放曲线和庆大霉素的化学变化，辐照处理似乎更适合于胶原蛋白/庆大霉素负载的PLGA微粒复合物。(c)2005 Elsevier B. V.保留所有权利。
In order to achieve implants which provide sustained release of gentamicin, microparticles based on a 50/50 Resomer (R) 503/Resomer (R) 502H blend were combined with collagen in order to achieve their fixation and to utilize the favorable effect of collagen on wound healing, Ethylene oxide treatment as well as beta- and gamma-irradiation were tested for sterilization of the collagen/PLGA-microparticle composite. All methods resulted in a decrease of molecular weight and glass transition temperature of polymer raw material and microparticles. In addition, ethylene oxide treatment yielded aggregation of microparticles leading to a substantial increase in the initially liberated gentamicin dose. Furthermore, chemical changes of gentamicin after ethylene oxide sterilization could be identified using NMR spectroscopy. Despite a decrease in the molecular weight and glass transition temperature after irradiation, neither morphological changes of the composites nor changes regarding the gentamicin release profile from beta- and gamma-sterilized material were observed. Free radicals, which could only be detected in gentamicin drug substance and at marginal level in gentamicin-loaded MPs, disappeared within 4 weeks. Additional microbiological testing verified the microbiological activity of gentamicin liberated from P-sterilized composites. Storage of P-sterilized composite at 4 degrees C/35% r.h. for 3 months did not influence morphology, molecular weight, glass transition temperature, and release profiles of microparticles and composites. However, at 25 degrees C/60% r.h. and 40 degrees C/75% r.h. a marked decrease in molecular weight and glass transition temperature resulted. This effect was due to a higher humidity, water uptake into polymers, and subsequent hydrolysis of polymers and microparticles, which was more pronounced for RG 502H because of its hydrophilicity. Upon storage at 25 degrees C/60% r.h. and 40 degrees C/75% r.h. particles collapsed resulting in an increased gentamicin liberation. Thus, all sterilization techniques have their pros and cons, but based on drug release profile and chemical changes of gentamicin irradiation treatment appears to be more suitable for collagen/gentamicin-loaded PLGA microparticle composites. (c) 2005 Elsevier B.V. All rights reserved.