Chitosan nanoparticle antigen uptake in epithelial monolayers can predict mucosal but not systemic in vivo immune response by oral delivery

Cole, Hannah L.; Bryan, Donna; Lancaster, Lorna; Mawas, Fatme; Vllasaliu, Driton

doi:10.1016/j.carbpol.2018.02.084

Cited by 31 publications

(17 citation statements)

References 31 publications

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“…Hannah et al reported a chitosan-based OVA antigen oral delivery system, after four times administration and 35 day immunization, CS-encapsulated OVA, to induce 2-fold mucosal (IgA) immune response compared with the OVA group, while immunization with CS-OVA failed to increase the anti-OVA IgG response. 45 By comparison, based on our in vitro studies using BSA-FITC as a model ( Figures 3 – 5 ), we can attribute the enhanced immune response observed for the NP system to the prevention of OVA degradation in the acidic conditions of the gastric fluid due to protection by the alginate coating and facilitated cellular uptake of OVA by the intestine cells aided by the chitosan coating.…”

Section: Results and Discussionmentioning

confidence: 93%

Enhanced Oral Vaccine Efficacy of Polysaccharide-Coated Calcium Phosphate Nanoparticles

et al. 2020

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Oral administration of vaccines has been limited due to low immune response compared to parenteral administration. Antigen degradation in the acidic gastrointestinal environment (GI), mucus barriers, and inefficient cellular uptake by immune cells are the major challenges for oral vaccine delivery. To solve these issues, the current study investigates calcium phosphate nanoparticles (CaP NPs) coated with polysaccharides as nanocarriers for oral protein antigen delivery. In this design, the CaP NP core had an optimized antigen encapsulation capacity of 90 mg (BSA-FITC)/g (CaP NPs). The polysaccharides chitosan and alginate were coated onto the CaP NPs to protect the antigens against acidic degradation in the GI environment and enhance the immune response in the small intestine. The antigen release profiles showed that alginate-chitosan-coated CaP NPs prevented antigen release in a simulated gastric fluid (pH 1.2), followed by sustained release in simulated intestinal (pH 6.8) and colonic (pH 7.4) fluids. Cellular uptake and macrophage stimulation data revealed that the chitosan coating enhanced antigen uptake by intestine epithelia cells (Caco-2) and macrophages and improved surface expression of costimulatory molecules on macrophages. In vivo test further demonstrated that oral administration of alginate-chitosan-coated CaP@OVA NPs significantly enhanced the mucosal IgA and serum IgG antibody responses as compared to naked OVA, indicating that the CaP-Chi-Alg nanoparticle can potentially be used as a promising oral vaccine delivery system.

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Section: Results and Discussionmentioning

confidence: 93%

Enhanced Oral Vaccine Efficacy of Polysaccharide-Coated Calcium Phosphate Nanoparticles

et al. 2020

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“…Various studies have demonstrated the activation of the dendritic cells, macrophages, and lymphocytes by the chitosan-mediated oral vaccine delivery system. 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].…”

Section: Current Oral Vaccine Delivery Systemsmentioning

confidence: 99%

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

et al. 2018

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Most currently available commercial vaccines are delivered by systemic injection. However, needle-free oral vaccine delivery is currently of great interest for several reasons, including the ability to elicit mucosal immune responses, ease of administration, and the relatively improved safety. This review summarizes the biological basis, various physiological and immunological barriers, current delivery systems with delivery criteria, and suggestions for strategies to enhance the delivery of oral vaccines. In oral vaccine delivery, basic requirements are the protection of antigens from the GI environment, targeting of M cells and activation of the innate immune response. Approaches to address these requirements aim to provide new vaccines and delivery systems that mimic the pathogen’s properties, which are capable of eliciting a protective mucosal immune response and a systemic immune response and that make an impact on current oral vaccine development.

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“…Chitosan (CS), a natural polysaccharide derived from the partial deacetylation of chitin, has been widely used in gene delivery. CS is uniquely suited for oral delivery due to its mucoadhesive and epithelial permeation properties [11,12]. The addition of mannose to the trimethyl-CS allows the NP delivery system to target intestinal macrophages.…”

Section: Oral Gene Delivery For Gene Therapy Applicationsmentioning

confidence: 99%

Oral non-viral gene delivery for applications in DNA vaccination and gene therapy

Farris

Sanderfer

Lampe

et al. 2018

Current Opinion in Biomedical Engineering

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Non-viral gene delivery via the oral route is a promising strategy for improving outcomes of DNA vaccination and gene therapy applications. Unlike traditional parenteral administration routes, the oral route is a non-invasive approach that lends itself to high patient compliance and ease of dosing. Moreover, oral administration allows for both local and systemic production of therapeutic genes or, in the case of DNA vaccination, mucosal and systemic immunity. However, the oral route presents distinct challenges and barriers to achieving successful gene delivery. Oral non-viral gene delivery systems must be able to survive the harsh and variable environments (e.g. acidic pH, degrading enzymes, mucus layer) encountered during transit through the gastrointestinal tract, while still allowing for efficient transgene production at sites of interest. These barriers present unique design challenges for researchers in material selection and in improving the transfection efficiency of orally delivered genes. This review provides an overview of advancements in the design of oral non-viral gene delivery systems, and highlights recent and important developments towards improving orally delivered genes for applications in gene therapy and DNA vaccination.

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Chitosan nanoparticle antigen uptake in epithelial monolayers can predict mucosal but not systemic in vivo immune response by oral delivery

Cited by 31 publications

References 31 publications

Enhanced Oral Vaccine Efficacy of Polysaccharide-Coated Calcium Phosphate Nanoparticles

Enhanced Oral Vaccine Efficacy of Polysaccharide-Coated Calcium Phosphate Nanoparticles

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

Oral non-viral gene delivery for applications in DNA vaccination and gene therapy

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