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.

Experimental Evaluation of the Transport Mechanisms of PoIFN-α in Caco-2 Cells

“…However, the FITC signals were not strong. It was likely due to the poor permeability for protein drugs (Liu et al, 2016 ). Moreover, it might also explain the low bioavailability of protein drugs.…”

Polymeric nanoparticle vaccines to combat emerging and pandemic threats

“…As chitosan is only soluble in acidic media with pH < 5 due to its high density of acetylated monomers, chitosan can be deacytelated, and its increasing degree of deacetylation is correlated to the increasing cationic density and hence solubility [ 41 ]. Another way to increase solubility of chitosan is by modifying its amino groups, forming trimethyl chitosan (TMC) [ 166 ], chitosan lactate [ 167 ], or oleyl-carboxymethy-chitosan (OCMCS) [ 168 ]. This cationic property of chitosan makes it easier to encapsulate anionic antigens [ 146 , 169 ] and nucleic acids [ 167 ], and other negatively charged biopolymers [ 170 ].…”

“…This cationic property of chitosan makes it easier to encapsulate anionic antigens [ 146 , 169 ] and nucleic acids [ 167 ], and other negatively charged biopolymers [ 170 ]. Additionally, due to their mucoadhesiveness, chitosan based nanoparticles have been used for mucosal delivery [ 166 , [168] , [169] , [170] , [171] ], which demonstrated enhanced DC uptake as well as promoted the opening of tight epithelial cell junctions in the mucosal tissues for paracellular transport of the antigen [ 172 ]. For example, intranasal administration of TMC nanoparticles containing lipopeptide antigens against group A Streptococcus (GAS) showed enhanced humoral immunity in mice, producing antibodies with high opsonic activity against clinical GAS strains [ 166 ].…”

Oral Vaccine Delivery for Intestinal Immunity—Biological Basis, Barriers, Delivery System, and M Cell Targeting

“…The formulation of chitosan-based nanoparticles has been developed by either chemical modification or complexation with oppositely charged molecules through electrostatic interactions [86,87]. With its nontoxicity, biodegradability, biocompatibility, and bio-adhesion ability, current chitosan applications still faced several challenges, such as water insolubility at physiological pH and easy degradation in acidic media, such as the GI tract [79,86,88,89,90]. Beta-glucans are one of the best candidates for oral vaccine delivery, which can provide target delivery to APCs and generally recognized as safe (GRAS).…”