title: Antigen-conjugated N-trimethylaminoethylmethacrylate chitosan nanoparticles induce strong immune responses after nasal administration.
abstract: OBJECTIVE
  Antigens were conjugated on the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles to induce systemic and mucosal immune responses after nasal immunization.
  
  
  METHODS
  TMC was synthesized by free radical polymerization and blank nanoparticles were prepared by ionic crosslinking of TMC and sodium tripolyphosphate. The model antigen (ovalbumin) was conjugated on the surface of blank nanoparticles (OVA-NP) through thioester bond formation. The cellular uptake of OVA-NP was investigated in Raw 264.7 macrophages and biodistribution of antigens was studied by the radioiodine labeling method. The immunological effects were evaluated by nasal administration of OVA-NP to Balb/C mice. The transport mechanism and nasal toxicity of OVA-NP were studied in rats.
  
  
  RESULTS
  The cellular uptake of OVA-NP was significantly higher than that of ovalbumin-encapsulated nanoparticles (NPe) after 30 min. Nasally administered OVA-NP showed higher transport of antigens to cervical lymph nodes with higher targeting efficiency than all other groups. Compared with NPe, OVA-NP induced much higher levels of systemic and mucosal immune responses in Balb/C mice after three nasal immunizations. Ex vivo culturing of nasopharynx-associated lymphoid tissue (NALT) confirmed its participation in nasal immunization. The transport mechanism study revealed that OVA-NP can be transported across the nasal epithelium through glands and may be taken up in NALT through M cells. OVA-NP did not induce obvious toxicity to nasal mucosa or hemolysis in animals.
  
  
  CONCLUSIONS
  The present study demonstrated that the conjugation of TMC nanoparticles with antigens is an effective strategy for nasal vaccination.
authors: Key Laboratory of Smart Drug Delivery (Fudan University) Ministry of Education, Shanghai, People's Republic of China, 201203.
authors: Qingfeng
authors: Q
authors: Liu
authors: Xiaoyao
authors: X
authors: Zheng
authors: Chi
authors: C
authors: Zhang
authors: Xiayan
authors: X
authors: Shao
authors: Xi
authors: X
authors: Zhang
authors: Qizhi
authors: Q
authors: Zhang
authors: Xinguo
authors: X
authors: Jiang
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D002460:Cell Line; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D004339:Drug Compounding; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D009305:Nasopharynx / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008689:Methacrylates; C000601247:N-trimethylaminoethylmethacrylate chitosan; D010047:Ovalbumin; D048271:Chitosan