title: Development of a pH-responsive particulate drug delivery vehicle for localized biologic therapy in inflammatory bowel disease.
abstract: The treatment of inflammatory bowel disease (IBD) recently has been revolutionized by the introduction of protein-based biologic therapies. However, biologic therapy is complicated by the requirement for administration with a needle, systemic side effects, and high cost. Particulate drug delivery systems have been shown to deliver drugs locally to the intestinal mucosa via oral administration. However, these systems have been largely unexplored for the delivery of biologics due to harsh particle fabrication conditions and the tendency of many particulate formulations to dissolve in the acidic upper GI tract. We have, therefore, fabricated an inexpensive and non-toxic novel microparticle capable of encapsulating proteins. We establish that the particle retains its contents at acidic pH and releases them at neutral pH. We also demonstrate particulate encapsulation of interleukin-10 (IL-10), a protein relevant to the treatment of IBD, at an encapsulation efficiency of 14.3 percent. Such a vehicle is promising for its oral route of administration and potential to decrease side effects and increase potency of biologics.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, USA.
authors.forename: Noah A
authors.initials: NA
authors.lastname: Capurso
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Fahmy
mesh_terms: D000284:Administration, Oral; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage / Q000648:ultrastructure; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D011109:Polymethacrylic Acids; D016753:Interleukin-10; C038300:methylmethacrylate-methacrylic acid copolymer