用多糖水凝胶靶向结肠的载有药物的纳米颗粒可在小鼠模型中减少结肠炎。,Gastroenterology

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用多糖水凝胶靶向结肠的载有药物的纳米颗粒可在小鼠模型中减少结肠炎。
Gastroenterology ( IF 25.7 ) Pub Date : 2009-11-17 , DOI: 10.1053/j.gastro.2009.11.003
Hamed Laroui ₁ , Guillaume Dalmasso , Hang Thi Thu Nguyen , Yutao Yan , Shanthi V Sitaraman , Didier Merlin

Affiliation

背景与目的治疗炎症性肠病（IBD）的挑战之一是针对炎症部位。我们设计了纳米颗粒（NPs），将抗炎性三肽Lys-Pro-Val（KPV）递送至结肠，并评估了其在结肠炎小鼠模型中的治疗效果。方法采用双乳液/溶剂蒸发法合成NP。在合成过程的第一个乳液中，将KPV装入NP中。为了将KPV靶向结肠，将负载的NP（NP-KPV）封装到包含2种聚合物（藻酸盐和壳聚糖）的多糖凝胶中。在体外以及右旋糖酐硫酸钠诱导的结肠炎小鼠模型中确定了KPV负载的NP对炎症参数的影响。结果NP（400 nm）不会影响细胞活力或屏障功能。溶胀度研究表明，含有葡聚糖-荧光素异硫氰酸酯标记的NP的藻酸盐-壳聚糖水凝胶在结肠中塌陷。传递后，NP在结肠细胞的封闭区域内或内部迅速释放KPV。与单独暴露于NPs的Caco2-BBE（刷状边界肠上皮细胞）细胞相比，暴露于脂多糖的炎症反应以剂量依赖性方式降低。与仅给予DSS的小鼠相比，给予右旋糖酐硫酸钠（DSS）和NP-KPV的小鼠免受炎症和组织学参数的影响。结论纳米颗粒是一种通用的药物输送系统，可以克服生理障碍并将抗炎药（例如肽KPV）靶向至发炎区域。通过使用NP，可以以12的浓度输送KPV 比KPV游离溶液低000倍，但疗效相似。封装的载有药物的NP的给药是一种治疗IBD的新方法。

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Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model.

BACKGROUND & AIMS One of the challenges to treating inflammatory bowel disease (IBD) is to target the site of inflammation. We engineered nanoparticles (NPs) to deliver an anti-inflammatory tripeptide Lys-Pro-Val (KPV) to the colon and assessed its therapeutic efficacy in a mouse model of colitis. METHODS NPs were synthesized by double-emulsion/solvent evaporation. KPV was loaded into the NPs during the first emulsion of the synthesis process. To target KPV to the colon, loaded NPs (NP-KPV) were encapsulated into a polysaccharide gel containing 2 polymers: alginate and chitosan. The effect of KPV-loaded NPs on inflammatory parameters was determined in vitro as well as in the dextran sodium sulfate-induced colitis mouse model. RESULTS NPs (400 nm) did not affect cell viability or barrier functions. A swelling degree study showed that alginate-chitosan hydrogel containing dextran-fluorescein isothiocyanate-labeled NPs collapsed in the colon. Once delivered, NPs quickly released KPV on or within the closed area of colonocytes. The inflammatory responses to lipopolysaccharide were reduced in Caco2-BBE (brush border enterocyte) cells exposed to NP-KPV compared with those exposed to NPs alone, in a dose-dependent fashion. Mice given dextran sodium sulfate (DSS) followed by NP-KPV were protected against inflammatory and histologic parameters, compared with mice given only DSS. CONCLUSIONS Nanoparticles are a versatile drug delivery system that can overcome physiologic barriers and target anti-inflammatory agents such as the peptide KPV to inflamed areas. By using NPs, KPV can be delivered at a concentration that is 12,000-fold lower than that of KPV in free solution, but with similar therapeutic efficacy. Administration of encapsulated drug-loaded NPs is a novel therapeutic approach for IBD.

更新日期：2009-11-10

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