title: M-cell targeted polymeric lipid nanoparticles containing a Toll-like receptor agonist to boost oral immunity.
abstract: Oral delivery of antigens is patient-friendly and efficient way of treating intestinal infections. However, the efficacy of oral vaccines is limited by degradation in the gastrointestinal (GI) tract and poor absorption by enterocytes and antigen-presenting cells (APC). Here we report ulex europaeus agglutinin-1 (UEA-1) conjugated poly (D,L-lactide-co-glycolide) (PLGA)-lipid nanoparticles (NP) containing a Toll-like receptor (TLR)-agonist monophosphoryl lipid A (MPL) as an oral vaccine delivery system. The uniform-sized PLGA-lipid NPs (simplified as lipid NPs) were produced by the premix membrane emulsification method. They can protect the entrapped model antigen ovalbumin (OVA) from exposure to the GI tract and release the OVA in a controlled manner. With UEA-1 and MPL modification, the UEA-MPL/lipid NPs can be effectively transported by M-cells and captured by mucosal dendritic cells (DCs). After in vivo vaccination, the OVA-UEA-MPL/lipid NPs stimulated the most effective mucosal IgA and serum IgG antibodies during the oral formulations. These results suggest that this MPL containing M-cell targeted lipid NP can potentially be used as a universally robust oral vaccine delivery system.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China; National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Ma
authors.affiliation: National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Lianyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Tingyuan
authors.initials: T
authors.lastname: Yang
authors.affiliation: National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, PR China. Electronic address: ghma@home.ipe.ac.cn.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China. Electronic address: silingwang@syphu.edu.cn.
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D018938:Caco-2 Cells; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007422:Intestines / Q000276:immunology; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D037121:Plant Lectins / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D051193:Toll-Like Receptors / Q000819:agonists; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008050:Lipid A; D037121:Plant Lectins; D051193:Toll-Like Receptors; C036850:Ulex europaeus lectins; D011100:Polyglycolic Acid; D010047:Ovalbumin; C048436:monophosphoryl lipid A
keywords: M-cell targeting; Oral delivery; Polymeric lipid nanoparticles; Toll-like receptor agonist; Vaccine