Preparation and in vitro analysis of microcapsule thalidomide formulation for targeted suppression of TNF-alpha.
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.
Metz
Terrence
T
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.
Haque
Tasima
T
Chen
Hongmei
H
Prakash
Satya
S
Amre
Devendra
D
Das
Sujata K
SK
D000464:Alginates / Q000032:analysis; D000818:Animals; D002214:Capsules; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000032:analysis; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011107:Polylysine / Q000031:analogs & derivatives / Q000032:analysis; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D013792:Thalidomide / Q000008:administration & dosage / Q000032:analysis*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000464:Alginates; D002214:Capsules; D007166:Immunosuppressive Agents; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha; C051546:alginate-polylysine-alginate; D011107:Polylysine; D013792:Thalidomide