Liggins R T, Cruz T, Min W, Liang L, Hunter W L, Burt H M
Angiotech Pharmaceuticals Inc., Vancouver, British Columbia, Canada.
Inflamm Res. 2004 Aug;53(8):363-72. doi: 10.1007/s00011-004-1273-1. Epub 2004 Aug 10.
To assess the biocompatibility of controlled release microspheres prepared from different polymeric biomaterials in various size ranges in rabbit synovial joints and based on these data, design and evaluate the efficacy of an intra-articular, paclitaxel-loaded microspheres formulation in rabbit models of arthritis.
Paclitaxel-loaded microspheres of poly(lactide-co-glycolide) (PLGA), poly(L-lactic acid) (PLA) and poly(caprolactone) (PCL) were prepared in different size ranges and inflammatory responses monitored following injection into healthy rabbit joints. The efficacy of 20% paclitaxel-loaded PLA microspheres (35-105 microm size range) injected intra-articularly into antigen and carrageenan induced rabbit models of arthritis was monitored.
Polymeric microspheres in the 35-105 microm size range were biocompatible whereas smaller microspheres (1-20 microm) produced an inflammatory response. Efficacy studies showed that injection of 20% paclitaxel-loaded PLA microspheres significantly reduced all measures of inflammation in the antigen arthritis rabbit model.
Paclitaxel-loaded PLA microspheres in the 35-105 microm size range, released paclitaxel in a controlled manner over several weeks, and may be a potential formulation for the intra-articular treatment of inflammation in arthritic conditions.
评估由不同高分子生物材料制备的不同尺寸范围的控释微球在兔滑膜关节中的生物相容性，并基于这些数据，设计并评估一种关节内注射的载紫杉醇微球制剂在兔关节炎模型中的疗效。
制备不同尺寸范围的聚（丙交酯-共-乙交酯）（PLGA）、聚（L-乳酸）（PLA）和聚己内酯（PCL）载紫杉醇微球，并在注射到健康兔关节后监测炎症反应。监测关节内注射20%载紫杉醇PLA微球（尺寸范围为35-105微米）对抗原和角叉菜胶诱导的兔关节炎模型的疗效。
尺寸范围为35-105微米的高分子微球具有生物相容性，而较小的微球（1-20微米）会产生炎症反应。疗效研究表明，注射20%载紫杉醇PLA微球可显著降低抗原性关节炎兔模型中的所有炎症指标。
尺寸范围为35-105微米的载紫杉醇PLA微球在数周内以可控方式释放紫杉醇，可能是一种用于关节内治疗关节炎炎症的潜在制剂。
