Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum
Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum
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DOI：
10.1002/jbm.a.30654
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Langer, R
中科院分区：
文献类型：
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作者：
Kohane, DS;Tse, JY;Langer, R
药物递送到腹膜受到快速清除的阻碍，并且可以通过应用控制释放技术来改善。我们研究了聚乳酸-羟基乙酸共聚物（PLGA）的微米和纳米颗粒用于腹膜的适用性，PLGA是一种生物可降解聚合物，通常具有良好的生物相容性，常用于药物控释。我们将直径为5-250 μ m的90 kDa PLGA微粒注射到小鼠腹膜中，剂量为10-100 mg（每组n = 3-5）。我们发现注射后2周聚合物残留和粘连的发生率很高（例如，50毫克的5 μ m微粒引起83%的动物粘连）。组织学检查显示慢性炎症，异物巨细胞突出，颗粒直径> 5 μ m。由54、57和10 kDa PLGA（伽马辐照）制成的5微米微球引起的粘连较少（1.6.7%），残留物发生率相似。90 kDa PLGA的纳米颗粒（265 nm）也引起少得多的粘连（6.3%的动物），可能是因为它们在2天内从腹膜中清除，并隔离在脾脏和肝脏中，其中注意到泡沫状巨噬细胞。灭菌技术对粘连形成发生率的影响也进行了研究。(c)2006 Wiley Periodicals，Inc.
Drug delivery to the peritoneum is hampered by rapid clearance, and could be improved by application of controlled release technology. We investigated the suitability for peritoneal use of micro- and nanoparticles of poly(lactic-co-glycolic) acid (PLGA), a biodegradable polymer with generally excellent biocompatibility commonly used for controlled drug release. We injected 90 kDa PLGA microparticles, 5-250 mu m in diameter, into the murine peritoneum, in dosages of 10-100 mg (n = 3-5 per group). We found a high incidence of polymeric residue and adhesions 2 weeks after injection (e.g., 50 mg of 5-mu m microparticles caused adhesions in 83% of animals). Histology revealed chronic inflammation, with foreign body giant cells prominent with particles > 5 mu m in diameter. Five micrometer microspheres made from 54, 57, and 10 kDa PLGA (gamma irradiated) caused fewer adhesions (1.6.7%) with a similar incidence of residue. Nanoparticles (265 nm) of 90 kDa PLGA also Caused much fewer adhesions (6.3% of animals), possibly because they were cleared from the peritoneum within 2 days, and sequestered in the spleen and liver, where foamy macrophages were noted. The effect of sterilization technique on the incidence of adhesion formation is also studied. (c) 2006 Wiley Periodicals, Inc.