title: A Thermo-Sensitive Delivery Platform for Topical Administration of Inflammatory Bowel Disease Therapies.
abstract: Systemic therapies for inflammatory bowel disease are associated with an increased risk of infections and malignancies. Topical therapies reduce systemic exposure, but can be difficult to retain or have limited proximal distribution. To mitigate these issues, we developed a thermo-sensitive platform, using a polymer-based system that is liquid at room temperature but turns into a viscous gel on reaching body temperature. After rectal administration to mice with dextran sulfate sodium-induced colitis, the platform carrying budesonide or mesalamine becomes more viscoelastic near body temperature. Mice given the drug-containing platform gained more weight and had reduced histologic and biologic features of colitis than mice given the platform alone or liquid drugs via enema. Image analysis showed that enemas delivered with and without the platform reached similar distances in the colons of mice, but greater colonic retention was achieved by using the platform.
authors: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California. Electronic address: sidsinha@stanford.edu.
authors: Sidhartha R
authors: SR
authors: Sinha
authors: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California.
authors: Linh P
authors: LP
authors: Nguyen
authors: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, California.
authors: Mohammed
authors: M
authors: Inayathullah
authors: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, California.
authors: Andrey
authors: A
authors: Malkovskiy
authors: Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
authors: Frezghi
authors: F
authors: Habte
authors: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, California. Electronic address: jayraja@stanford.edu.
authors: Jayakumar
authors: J
authors: Rajadas
authors: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California. Electronic address: aidah@stanford.edu.
authors: Aida
authors: A
authors: Habtezion
mesh_terms: D000285:Administration, Rectal; D000287:Administration, Topical; D000818:Animals; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains
chemical_list: D016264:Dextran Sulfate
keywords: Drug Delivery; Mouse Model of IBD; TDDP; Technology