Hickey T, Kreutzer D, Burgess D J, Moussy F
Center for Biomaterials, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06032-1615, USA.
J Biomed Mater Res. 2002 Aug;61(2):180-7. doi: 10.1002/jbm.10016.
The purpose of this research effort was to evaluate in vivo a newly developed dexamethasone/PLGA microsphere system designed to suppress the inflammatory tissue response to an implanted device, in this case a biosensor. The microspheres were prepared using an oil/water (O/W) emulsion technique. The microsphere system was composed of drug-loaded microspheres (including newly formulated and predegraded microspheres) and free dexamethasone. The combination of the drug and drug-loaded microspheres provided burst release of dexamethasone followed by continuous release from days 2-14. Continuous release to at least 30 days was achieved by mixing predegraded and newly formulated microspheres. The ability of our mixed microsphere system to control tissue reactions to an implant then was tested in vivo using cotton thread sutures to induce inflammation subcutaneously in Sprague-Dawley rats. Two different in vivo studies were performed, the first to find the dosage level of dexamethasone that effectively would suppress the acute inflammatory reaction and the second to show how effective the dexamethasone delivered by PLGA microspheres was in suppressing chronic inflammatory response to an implant. The first in vivo study showed that 0.1 to 0.8 mg of dexamethasone at the site minimized the acute inflammatory reaction. The second in vivo study showed that our mixed microsphere system suppressed the inflammatory response to an implanted suture for at least 1 month. This study has proven the viability of microsphere delivery of an anti-inflammatory to control the inflammatory reaction at an implant site.
本研究旨在对一种新开发的地塞米松/聚乳酸-羟基乙酸共聚物（PLGA）微球系统进行体内评估，该系统旨在抑制对植入装置（在本案例中为生物传感器）的炎症组织反应。微球采用油/水（O/W）乳液技术制备。微球系统由载药微球（包括新配制的和预降解的微球）和游离地塞米松组成。药物与载药微球的组合使地塞米松实现突释，随后在第2至14天持续释放。通过混合预降解微球和新配制微球实现了至少30天的持续释放。然后，我们使用棉线缝合在Sprague-Dawley大鼠皮下诱导炎症，在体内测试了混合微球系统控制组织对植入物反应的能力。进行了两项不同的体内研究，第一项研究旨在确定能有效抑制急性炎症反应的地塞米松剂量水平，第二项研究旨在表明PLGA微球递送的地塞米松在抑制对植入物的慢性炎症反应方面的效果如何。第一项体内研究表明，在植入部位使用0.1至0.8毫克地塞米松可使急性炎症反应最小化。第二项体内研究表明，我们的混合微球系统对植入缝线的炎症反应的抑制作用至少持续1个月。本研究证明了微球递送抗炎药物以控制植入部位炎症反应的可行性。
