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室温下使用可生物降解聚合物颗粒设计和评估抗生素释放自组装支架。

Design and evaluation of antibiotic releasing self- assembled scaffolds at room temperature using biodegradable polymer particles.

机构信息

Product Development Cell, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.

出版信息

Int J Pharm. 2017 Mar 30;520(1-2):284-296. doi: 10.1016/j.ijpharm.2017.01.071. Epub 2017 Feb 6.

Abstract

Biodegradable polymer-based drug-eluting implants offer many advantages such as predictable drug release kinetics, safety, and acceptable drug loading under ambient conditions. Herein, we describe fabrication and evaluation of antibiotic loaded scaffolds for localized delivery and tissue engineering applications. PDLLA particles entrapping gentamycin were formulated using solvent evaporation method and used for scaffold fabrication. Optimization of formulation parameters such as pH of the internal aqueous phase and combination of excipients like glycerol, polyvinyl alcohol (PVA) resulted in high entrapment efficiencies up to 96% of gentamicin in particles with drug load of 16-18μg/mg of polymer particles. These microparticles were fused in presence of methanol at ambient temperatures to form scaffolds of different geometry having reasonable mechanical strength. Porosity of these scaffolds was found to be more than 80%. Antibiotic released from the scaffolds was found to be bioactive as tested against Staphylococcus aureus and the release pattern was biphasic over a period of one week. The scaffolds were found to be non-toxic to murine fibroblasts cultures in vitro as well as to mice upon subcutaneous implantation. This method provides a novel and easy way of fabricating antibiotic loaded polymer scaffolds for varieties of applications.

摘要

基于可生物降解聚合物的药物洗脱植入物具有许多优点,如可预测的药物释放动力学、安全性和在环境条件下可接受的药物负载。本文描述了抗生素负载支架的制备和评估,用于局部递送和组织工程应用。使用溶剂蒸发法制备包载庆大霉素的 PDLLA 颗粒,并用于支架的制备。通过优化制剂参数,如内水相的 pH 值以及甘油、聚乙烯醇 (PVA) 等赋形剂的组合,可以使庆大霉素的包封效率高达 96%,药物载量为 16-18μg/毫克聚合物颗粒。这些微球在环境温度下在甲醇的存在下融合,形成具有合理机械强度的不同几何形状的支架。这些支架的孔隙率超过 80%。从支架中释放的抗生素被证明是具有生物活性的,因为它可以对抗金黄色葡萄球菌,并且在一周的时间内呈现出双相释放模式。体外实验表明,支架对鼠成纤维细胞培养物以及皮下植入的小鼠均无毒性。这种方法为各种应用提供了一种制造负载抗生素的聚合物支架的新颖而简单的方法。

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