title: Nano-polyplex based on oleoyl-carboxymethy-chitosan (OCMCS) and hyaluronic acid for oral gene vaccine delivery.
abstract: Here we described nano-polyplexes (NPs) made of oleoyl-carboxymethy-chitosan (OCMCS)/hyaluronic acid (HA) as novel potential carriers for oral gene vaccines delivery. Aerolysin gene (aerA) of Aeromonas hydrophila as microbial antigen was efficiently loaded to form OCMCS-HA/aerA (OHA) NPs. OHA NPs performed the optimal parameters, i.e. smallest (154.5±9.4nm), positive charged (+7.9±0.5mV) and monodispersed system with the N/P ratio of 5 and OCMCS/HA weight ratio of 4. Upon the introduction of HA, OHA NPs was beneficial for the DNA release in intestinal environments in comparison to OA NPs. The mean fluorescence intensity detected in Caco-2 cells incubated with OHA NPs was about 2.5-fold higher than that of OA NPs; however, it decreased significantly in the presence of excess free HA. The OHA NPs and OA NPs decreased the transepithelial electric resistance (TEER) of Caco-2 monolayers obviously and induced increasing the apparent permeability coefficient (Papp) of DNA by 5.45-6.09 folds compared with free DNA. Significantly higher (P<0.05) antigen-specific antibodies were detected in serum after orally immunized with OHA NPs than that immunized with OA NPs and DNA alone in carps. These results enable the OHA NPs might resolve challenges arising from gastrointestinal damage to gene antigens, and offer an approach applicable for oral vaccination.
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, PR China. Electronic address: yaliu@ouc.edu.cn.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, PR China.
authors.forename: Fang-Qin
authors.initials: FQ
authors.lastname: Wang
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, PR China.
authors.forename: Zeana
authors.initials: Z
authors.lastname: Shah
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, PR China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Cheng
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Feng
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao, 266003, PR China. Electronic address: xgchen@ouc.edu.cn.
authors.forename: Xi-Guang
authors.initials: XG
authors.lastname: Chen
mesh_terms: D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D019444:Vaccines, DNA; D006820:Hyaluronic Acid; D048271:Chitosan
keywords: Gene vaccine; HA; Nano-polyplex; Ocmcs; Oral delivery