Mimicking microbial strategies for the design of mucus-permeating nanoparticles for oral immunization

Abstract

Dealing with mucosal delivery systems means dealing with mucus. The name mucosa comes from mucus, a dense fluid enriched in glycoproteins, such as mucin, which main function is to protect the delicate mucosal epithelium. Mucus provides a barrier against physiological chemical and physical aggressors (i.e., host secreted digestive products such as bile acids and enzymes, food particles) but also against the potentially noxious microbiota and their products. Intestinal mucosa covers 400m(2) in the human host, and, as a consequence, is the major portal of entry of the majority of known pathogens. But, in turn, some microorganisms have evolved many different approaches to circumvent this barrier, a direct consequence of natural co-evolution. The understanding of these mechanisms (known as virulence factors) used to interact and/or disrupt mucosal barriers should instruct us to a rational design of nanoparticulate delivery systems intended for oral vaccination and immunotherapy. This review deals with this mimetic approach to obtain nanocarriers capable to reach the epithelial cells after oral delivery and, in parallel, induce strong and long-lasting immune and protective responses.

The effect of thiamine-coating nanoparticles on their biodistribution and fate following oral administration

“…In addition, from a microscopic point of view ( Figure 6), it was clear that bare nanoparticles displayed a different behaviour than thiamine-nanoparticles (T-NPA and T-NPB). Thus, within the gut mucosa, NP was localized in the protective mucus layer confirming their mucoadhesive capability (Arbós et al, 2002;Gamazo et al, 2015). On the contrary, thiamine nanoparticles appeared to be capable of reaching the intestinal epithelium, confirming their mucus permeating properties.…”

Vaccines againstTrichinella spiralis: Progress, challenges and future prospects

“…The particles can deliver the coated or “decorated” compounds or molecules to follicle associated epithelium (FAE, e.g., Peyer's patches), where covered with M cells, specialized for the antigen sampling (Pelaseyed et al., ). Oral delivery of nanocarriers can mimic microbial invasion to circumvent mucosal barriers to reach to the epithelial cells and induce the mucosal immunity and protective responses in a long term (Gamazo, Martín‐Arbella, Brotons, Camacho, & Irache, ). Utilization of nanoparticles or microparticles as delivery systems would protect pigs against T. spiralis infection in a lifelong period after a single immunization, which would be suitable for the free‐ranging pigs.…”

Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

“…[1][2][3][4][5] Besides all the advantages of the oral route, factors like low aqueous solubility of drugs, limited gastrointestinal (GI) absorption, rapid metabolism of drug, and low mucosal permeability play a major role in the disappointing in vivo results. [5][6][7][8] The intestinal mucosa plays an effective role as a physical barrier that covers the surfaces of the GI tract, allowing selective absorption of nutrients, electrolytes, and fluids, at the same time protecting the host from environmental pathogens.…”

“…18,19 In this context, mannosylated nanocarriers obtained by the decoration of particulates with mannose or its derivatives have been considered promising non-live vectors. 4,10,13,20 Moreover, M-cells may be exploited by some pathogenic microorganisms, such as Salmonella, Yersinia, Typhimurium (Salmonella typhimurium), Mycobacterium sp., and retrovirus, as a portal for the host organism. 11,12,21 M. leprae is an intracellular pathogen and the endocytic/phagocytic pathway may represent an interesting approach to allow targeted drug delivery intracellularly.…”

“…[5][6][7][8] The intestinal mucosa plays an effective role as a physical barrier that covers the surfaces of the GI tract, allowing selective absorption of nutrients, electrolytes, and fluids, at the same time protecting the host from environmental pathogens. 1,4,7,9 The first barrier encountered by such drugs is the mucus layer, which functions as a diffusional and enzymatic barrier. 10 After oral administration, a drug must infiltrate through the unstirred layer of mucus before reaching the surface of the intestinal epithelium, the second barrier.…”