Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics (original) (raw)
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Particle uptake by Peyer’s patches: a pathway for drug and vaccine delivery
Expert Opinion on Drug Delivery, 2004
Particle uptake by Peyer's patches offers the possibility of tailoring vaccines that can be delivered orally. However, particle uptake by the follicle-associated epithelium in the gastrointestinal tract depends on several different factors that are the physicochemical properties of the particles, the physiopathological state of the animal, the analytical method used to evaluate the uptake and finally the experimental model. These parameters do not allow a clear idea about the optimal conditions to target the Peyer's patches. The goal of this review is to clarify the role of each factor in this uptake.
European Journal of Pharmaceutics and Biopharmaceutics, 2005
Nano-and microparticles of poly(lactide-co-glycolide) (PLGA) were formulated using poly(vinyl alcohol) (PVA) or hydrophobically modified hydroxyethylcellulose (HMHEC) or polyethyleneimine (PEI) as stabilizers. The uptake by murine Peyer's patches (PPs) and the binding to Peyer's patches-free tissue (PPFT) of these particles was investigated using fluorescence microscopy providing qualitative information about the tissue distribution of particles. Observations of intestinal cryo-sections showed significant discrimination in the uptake by PP of nano-and microparticles. The uptake by PPs of PLGA-PVA and PLGA-HMHEC nano-and microparticles, of negative and neutral zeta potential, respectively, was comparable, whereas a smaller number was observed in the case of nano-and microparticles of PLGA-PEI, positively charged. Moreover, particle uptake by PPs appeared to be strongly size-dependent. The number of particles of mean diameter around 0.3 and 1 mm observed in PPs was much greater than that of particles of diameter average close to 3 mm. However, in all cases, particles were found in the PPFT for at least 48 h. In conclusion, regarding the tissue samples we have observed, it appeared that the uptake of particles by PPs and binding to PPFT could be influenced by the physicochemical properties of the particles but this may not have been true at all sites of the intestine and may differ between animals.
The gut wall provides an effective barrier against nanoparticle uptake
Beilstein Journal of Nanotechnology, 2014
Background: The omnipresence of nanoparticles (NPs) in numerous goods has led to a constant risk of exposure and inadvertent uptake for humans. This situation calls for thorough investigation of the consequences of NP intake. As the vast mucosa of the human gastrointestinal tract represents an attractive site of entry, we wanted to take a look on the fate that ingested NPs suffer in the gut. As a model to investigate NP uptake we used the isolated perfused rat small intestine. Differently sized fluorescent latex particles were used as exemplary anthropogenic NPs.Results: The particles were administered as bolus into the isolated intestine, and samples from the luminal, vascular and lymphatic compartments were collected over time. NP amounts in the different fluids were determined by fluorescence measurements. No particles could be detected in the vascular and lymphatic system. By contrast a major amount of NPs was found in luminal samples. Yet, a substantial share of particles could...
Nanoparticles as carriers for oral peptide absorption: Studies on particle uptake and fate
Journal of Controlled Release, 1995
Previous work from our laboratories has provided quantitative proof of the importance of the gut associated lymphoid tissue (GALT) in the processes involved in the uptake of polystyrene nanoparticles delivered orally, and has confirmed the role of the Peyer's patches in the uptake of particles through the small intestine. In more recent work discussed here the role of lymphoid tissue in the large intestine has been demonstrated, a significant amount of the total uptake occurring in this region of the gut. Adsorption of poloxamers 188 and 407 onto 50 nm polystyrene nanopartictes inhibited uptake in the small intestine and reduced uptake from the large intestine, suggesting reduction in adhesion to GALT and other epithelial tissues in the presence of the poloxamer coating but also indirectly suggesting differences in the surface characteristics of lymphoid tissue at different sites in the gut. The covalent attachment of tomato (Lycopersicon esculentum) lectin molecules to the surface of 500 nm polystyrene particles had a significant effect not only on total uptake (well over a 10-fold increase in absorption over 'plain' particles after 5 days daily dosing) but on the locus of uptake, which is shifted from lymphoid to normal non-lymphoid intestinal tissue. We have demonstrated, therefore, both an increase and a decrease in absorption of nanoparticles from the gastro-intestinal tract and some, albeit serendipitous, control of the site of uptake and absorption, which should provide pointers for the future development of systems with optimal uptake characteristics.
It takes more than a coating to get nanoparticles through the intestinal barrier in vitro
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2016
Size and shape are crucial parameters which have impact on the potential of nanoparticles to penetrate cell membranes and epithelial barriers. Current research in nanotoxicology additionally focuses on particle coating. To distinguish between core- and coating-related effects in nanoparticle uptake and translocation, two nanoparticles equal in size, coating and charge but different in core material were investigated. Silver and iron oxide nanoparticles coated with poly (acrylic acid) were chosen and extensively characterized by small-angle x-ray scattering, nanoparticle tracing analysis and transmission electron microscopy (TEM). Uptake and transport were studied in the intestinal Caco-2 model in a Transwell system with subsequent elemental analysis. TEM and ion beam microscopy were conducted for particle visualization. Although equal in size, charge and coating, the behavior of the two particles in Caco-2 cells was different: while the internalized amount was comparable, only iron ...
A novel In Vitro Model for Studying Nanoparticle Interactions with the Small Intestine
EURO-NanoTox-Letters, 2016
Manufactured nanomaterials provide promising features for new technologies in cosmetic, food, and pharmaceutical applications. On the other hand, orally ingested nanomaterials/nanoparticles may interact with or enter intestinal cells via different mechanisms, resulting in possible injuries of the biological system. For that reason, the current study aims to provide useful information concerning physicochemical properties of nanoparticles with regard to cytotoxic effects and uptake mechanisms in the small intestine. Differently charged polystyrene nanoparticles were used and cytotoxicity and uptake were studied with an intestinal in vitro co-culture model, mimicking the villus epithelium and a triple-culture model recapitulating the follicle-associated epithelium. Mechanisms of cellular transport were investigated at 37°C and 4°C to verify that internalization mainly occurs energy-dependently. Chemical inhibitors (i.e., chlorpromazine, genistein, dynasore) were used to block dynamin-dependent endocytic pathways without affecting cell viability and membrane integrity. Qualification and quantification were performed via confocal microscopy and flow cytometry. Furthermore, co-localization studies with commonly used markers (i.e., transferrin, lactosylceramide) were carried out and co-localization was assessed via calculation of Pearson´s correlation coefficient and Mander´s overlap coefficient. The results show that size and surface chemistry play a crucial role in cytotoxic interactions and cellular uptake of nanoparticles (NPs). Independent of the surface charge, NPs strongly interact with intestinal mucus and are immobilized. Uptake predominantly occurs via M cells and is surface-charge dependent. Whereas negatively charged particles fail to enter cells, positive and neutral particles penetrate M cells energy-dependently. More precisely, both clathrin-and caveolae-mediated endocytosis are involved. It can be concluded that the presented system serves as a valuable tool to assess safety aspects of manufactured nanomaterials and hence, substantially contributes to nanosafety efforts.
Nanoparticulate drug-delivery systems: lymphatic uptake and its gastrointestinal applications
Journal of Applied Pharmaceutical Science, 2014
One of the important challenges of modern drug therapy is the optimization of the pharmacological action of a drug along with the reduction of its toxic side effects in vivo. One response is the use of drug carriers that can provide site specific or targeted drug delivery combined with optimal drug release profiles. Nanoparticulate systems (NPS) as a drug delivery system is an emerging field in medical sciences since they are believed to target the delivery of the drug in cells reduce dose and thus reduce side effects and dose related toxicities.The gastrointestinal tract (GIT) uptake of nanoparticulate systems is nowadays well accepted phenomenon. Uptake of Nanoparticulates from the gut can provide an additional drug administration route with its own pharmacokinetic parameters and specific drug-carrying ability. The drug is transported into the GIT by carriers whose physicochemical characteristics must be taken into account, although the physico-chemical and pharmacological characteristics of the drug remain intact. In this article we concentrate particularly on the translocation of NPS via the lymphatic system, and their use.