title: Layer-by-layer assembled milk protein coated magnetic nanoparticle enabled oral drug delivery with high stability in stomach and enzyme-responsive release in small intestine.
abstract: We report a novel drug delivery system composed of layer-by-layer (LBL) milk protein casein (CN) coated iron oxide nanoparticles. Doxorubicin (DOX) and indocyanine green (ICG) were selected as model drug molecules, which were incorporated into the inner polymeric layer, and subsequently coated with casein. The resulting casein coated iron oxide nanoparticles (CN-DOX/ICG-IO) were stable in the acidic gastric condition with the presence of gastric protease. On the other hand, the loaded drugs were released when the casein outer layer was gradually degraded by the intestinal protease in the simulated intestine condition. Such unique properties enable maintenance of the bioactivity of the drugs and thus enhance the drug delivery efficiency. Ex vivo experiments showed that the LBL CN-DOX-IO improved the translocation of DOX across microvilli and its absorption in the small intestine sacs. In vivo imaging of mice that were orally administered with these LBL CN-ICG-IO nanostructures further confirmed that the reported drug delivery vehicles could pass the stomach without significant degradation, and then accumulated in the small intestine. In addition, the magnetic iron oxide nanoparticle core offered an MRI contrast enhancing capability for in vivo imaging guided drug delivery. Therefore, the reported LBL CN-DOX/ICG-IO is a promising oral drug delivery nanoplatform, especially for drugs that are poorly soluble in water or degradable in the gastric environment.
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for Systems Imaging, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; The First Affiliated Hospital of Shenzhen University and The Second People's Hospital of Shenzhen, Shenzhen, Guangdong, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shu
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for Systems Imaging, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Ocean Nanotech LLC, Springdale, AR 72764, USA.
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Wang
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; Center for Systems Imaging, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: hmao@emory.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002364:Caseins / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008894:Milk Proteins / Q000737:chemistry*
chemical_list: D002364:Caseins; D058185:Magnetite Nanoparticles; D008894:Milk Proteins
keywords: Casein; Layer-by-layer; Magnetic resonance; Nanoparticles; Oral drug delivery