新型双亲性载药温敏凝胶IPF/PECT的实验研究

Investigation of a novel PECT based drug delivery system of IPF loaded amphiphilic thermosensitive hydrogel

目的:制备负载布洛芬(IPF)的新型温敏凝胶IPF/PECT,并探讨其在牙周局部缓释用药的可行性。方法:采用纳米沉淀技术制备IPF/PECT纳米粒(IPF/PECT NPs),将其冻干并用双蒸水溶解成凝胶制剂后,分别用TEM观察其纳米粒形貌;MTT法检测其生物相容性;ELISA法测定其体外细胞抗炎效果;于37℃下观察其液-胶转变情况及药物缓释特性。结果:IPF/PECT纳米粒径均匀,无明显聚合现象;用含不同浓度(0、200、400、800、1 200、1 600、2 000μg/m L)IPF/PECT的培养基培养牙龈成纤维细胞(HGFs)48 h后,各组间平均OD值两两相比差异均无统计学意义(P﹥0.05);在0.1μg/m L LPS刺激下同时加入60μg/m L的IPF或IPF/PECT,并与HGFs共同培养10、24、48、72 h后,各时间点的前列腺素E2(PGE2)浓度均为IPF/PECT组明显低于IPF组(P<0.05);IPF/PECT体外释放IPF可持续32 d以上,药物累积释放量达85%。结论:本实验所制备的新型双亲性载药温敏凝胶IPF/PECT具有良好的生物安全性和缓慢释药功能,其抗炎效果明显优于IPF水溶液。

AIM： To investigate the biosafety,anti-inflammatory effect and drug- release property of a novel PECT-based drug delivery system of ibuprofen（ IPF） loaded amphiphilic thermosensitive hydrogel. METHODS：IPF / PECT nanoparticles（ IPF / PECT NPs） were manufactured by nanoprecipitation,then the particles were freeze-dried and dissolved into double distilled water to become a liquid solution. The morphology of the particles was observed by TEM,the anti-inflammatory effect of IPF / PECT nanoparticles was examined by MTT and ELISA with a human gingival fibroblasts（ HGFs） based inflammation model. RESULTS： The particles were uniform- sized and no aggregation was observed. After loading different concentrations（ 0,200,400,800,1,200,1,600 and 2,000 μg / m L respectively） of IPF / PECT,the means of OD value of HGFs were 0. 29 ± 0. 01,0. 28 ± 0. 01,0. 29 ± 0. 02,0. 29 ±0. 03,0. 29 ± 0. 03,0. 29 ± 0. 03,and 0. 28 ± 0. 02 respectively（ between each 2 groups,P ﹥ 0. 05）. At every point- in- time,the IPF / PECT group showed lower PGE2 level than IPF group（ P〈0. 05）. The total release process could last for 32 days,with a cumulative release amount of 85%. CONCLUSION： The novel PECT- based drug delivery system is biocompatable with slow-releasing property and anti-inflammatory effect.