title: Zein-based oral drug delivery system targeting activated macrophages.
abstract: Reactive oxygen species (ROS) play an important role in the pathogenesis of rheumatoid arthritis (RA). ROS such as hydrogen peroxide and superoxide are overproduced by activated macrophages in RA. As scavengers of ROS, enzymatic proteins such as catalase and superoxide dismutase (SOD) have a great therapeutic potential; however, in vivo application is limited especially when they are orally administered. Although, the oral route is the most convenient for drug administration, therapeutic proteins are easily degraded in vivo by the harsh conditions of gastrointestinal (GI) tract. Here, we introduce a novel drug delivery system composed of zein, a plant storage protein derived from maize. We demonstrate that zein nanoparticles can protect therapeutic proteins, catalase and SOD, from the harsh conditions of GI tract. Folate-conjugated catalase or SOD in zein nanoparticles can target the activated macrophages and scavenge the ROS generated by macrophages in vitro. This novel drug delivery system will be applicable to other orally administered treatments based on the protective property in the harsh conditions of GI tract.
authors.affiliation: Department of Biomedical Engineering, Khalifa University of Science, Technology, and Research, PO Box 127788, Abu Dhabi, United Arab Emirates. sung.lee@kustar.ac.ae
authors.forename: Sungmun
authors.initials: S
authors.lastname: Lee
authors.forename: Noaf Salah Ali
authors.initials: NS
authors.lastname: Alwahab
authors.forename: Zainab Muhammad
authors.initials: ZM
authors.lastname: Moazzam
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D002374:Catalase / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004795:Enzyme Stability; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000737:chemistry; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D011489:Protein Denaturation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D015028:Zein / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D015028:Zein; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Inflammatory disease; Oral drug delivery; Reactive oxygen species; Zein