title: Screening of budesonide nanoformulations for treatment of inflammatory bowel disease in an inflamed 3D cell-culture model.
abstract: Drug formulation screenings for treatment of inflammatory bowel disease (IBD) are mostly conducted in chemically induced rodent models that represent acute injury-caused inflammation instead of a chronic condition. To accurately screen drug formulations for chronic IBD, a relevant model that mimics the chronic condition in vitro is urgently needed. In an effort to reduce and potentially replace this scientifically and ethically questionable animal testing for IBD drugs, our laboratory has developed an in vitro model for the inflamed intestinal mucosa observed in chronic IBD, which allows high-throughput screening of anti-inflammatory drugs and their formulations. The in vitro model consists of intestinal epithelial cells, human blood-derived macrophages, and dendritic cells that are stimulated by the inflammatory cytokine interleukin-1β. In this study, the model was utilized for evaluation of the efficacy and deposition of budesonide, an anti-inflammatory drug, in three different pharmaceutical formulations: (1) a free drug solution, (2) encapsulated into PLGA nanoparticles, and (3) encapsulated into liposomes. The in vitro model of the inflamed intestinal mucosa demonstrated its ability to differentiate therapeutic efficacy among the formulations while maintaining the convenience of conventional in vitro studies and adequately representing the complex pathophysiological changes observed in vivo.
authors: Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
authors: Fransisca
authors: F
authors: Leonard
authors: Hussain
authors: H
authors: Ali
authors: Eva-Maria
authors: EM
authors: Collnot
authors: Bart J
authors: BJ
authors: Crielaard
authors: Twan
authors: T
authors: Lammers
authors: Gert
authors: G
authors: Storm
authors: Claus-Michael
authors: CM
authors: Lehr
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D019819:Budesonide / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000633:toxicity; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry; D008081:Liposomes; D008264:Macrophages; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016209:Interleukin-8; D008081:Liposomes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019819:Budesonide