用于靶向抑制肿瘤坏死因子-α的微胶囊沙利度胺制剂的制备及体外分析

Preparation and in vitro analysis of microcapsule thalidomide formulation for targeted suppression of TNF-alpha.

作者信息

Metz Terrence, Haque Tasima, Chen Hongmei, Prakash Satya, Amre Devendra, Das Sujata K

机构信息

Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.

出版信息

Drug Deliv. 2006 Sep-Oct;13(5):331-7. doi: 10.1080/10717540500466097.

DOI:10.1080/10717540500466097

PMID:16877307

Abstract

Recent studies have implicated the cytokine tumor necrosis factor-alpha (TNF-alpha) in the inflammation associated with Crohn's disease (CD). Thalidomide has been shown to decrease this inflammation by the suppression of TNF-alpha secretion. However, side effects associated with thalidomide have precluded its widespread usage. In the present study we investigated the efficacy of a "targeted delivery approach" for thalidomide at the site of inflammation. We observed that alginate-poly-l-lysine-alginate (APA) polymer-based microcapsule formulations that encapsulate thalidomide could be designed. These capsules could be delivered at target sites where they almost entirely suppress TNF-alpha secretion in lipopolysaccharide activated RAW 264.7 macrophage cells in vitro. These findings indicate that targeted delivery of thalidomide using APA capsules could facilitate its usage in reducing the inflammation associated with chronic conditions such as Crohn's disease and ulcerative colitis.

摘要

最近的研究表明，细胞因子肿瘤坏死因子-α（TNF-α）与克罗恩病（CD）相关的炎症有关。沙利度胺已被证明可通过抑制TNF-α分泌来减轻这种炎症。然而，与沙利度胺相关的副作用使其无法广泛使用。在本研究中，我们调查了沙利度胺“靶向递送方法”在炎症部位的疗效。我们观察到，可以设计出基于海藻酸盐-聚-L-赖氨酸-海藻酸盐（APA）聚合物的微胶囊制剂来包裹沙利度胺。这些胶囊可以递送至靶部位，在体外脂多糖激活的RAW 264.7巨噬细胞中，它们几乎能完全抑制TNF-α分泌。这些发现表明，使用APA胶囊靶向递送沙利度胺有助于其用于减轻与诸如克罗恩病和溃疡性结肠炎等慢性疾病相关的炎症。