Oral nanoparticles

Martz, Lauren

doi:10.1038/scibx.2013.1371

Cited by 3 publications

(2 citation statements)

References 5 publications

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“…1 This challenge has been accentuated by Edith Mathiowitz: "Peptides need the protection of nanoparticles for stability through the GI tract". 2 Successful peroral administration of peptide and protein drugs requires sufficient protection of the drugs from enzyme degradation and from the complex physiological environment of the gastrointestinal tract, and this issue has not yet been satisfactorily resolved. Therefore, there is an urgent need to develop a delivery system that can protect such active biomolecules and ensure efficient targeting.…”

Section: Introductionmentioning

confidence: 99%

In situ self-assembly of peptides in glucan particles for macrophage-targeted oral delivery

Zhang

Zhao

et al. 2014

J. Mater. Chem. B

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Section: Introductionmentioning

confidence: 99%

In situ self-assembly of peptides in glucan particles for macrophage-targeted oral delivery

Zhang

Zhao

et al. 2014

J. Mater. Chem. B

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“…For the development of an oral delivery system with nanocarriers through electrostatic interaction, the effect of fluctuations in pH during gastrointestinal transit and serum in the systemic circulation should be considered as biochemical barriers [ 39 , 40 ]. Our simulated results under the physiological condition of pH fluctuations and serum concentration indicated that complex having over 50/1 ratio did not lose its stability and provided protection of its pDNA.…”

Section: Discussionmentioning

confidence: 99%

Antibody-mediated oral delivery of therapeutic DNA for type 2 diabetes mellitus

et al. 2018

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BackgroundDiabetes mellitus (DM) is a chronic progressive metabolic disease that involves uncontrolled elevation of blood glucose levels. Among various therapeutic approaches, GLP-1 prevents type 2 diabetes mellitus (T2DM) patients from experiencing hyperglycemic episodes. However, the short half-life (< 5 min) and rapid clearance of GLP-1 often limits its therapeutic use. Here, we developed an oral GLP-1 gene delivery system to achieve an extended antidiabetic effect.MethodsHuman IgG1 (hIgG1)-Fc-Arg/pDNA complexes were prepared by an electrostatic complexation of the expression plasmid with various ratios of the positively modified Fc fragments of an antibody (hIgG1-Fc-Arg) having a targeting ability to FcRn receptor. The shape and size of the complexes were examined by atomic force and field emission electron microscope. The stability of the complexes was tested in simulated gastrointestinal pH and physiological serum condition. Cellular uptake, transport, and toxicity of the complexes were tested in the Caco-2 cells. Biodistribution and antidiabetic effect of the complexes were observed in either Balb/c mice or Lepdb/db mice.ResultsA 50/1 ratio of the hIgG1-Fc-Arg/pDNA produced a complex structure having approximately 40 ~ 60 nm size and also demonstrated protection of pDNA in the complex from the physiological pH and serum conditions. Cellular uptake and transport of the complex were demonstrated in Caco-2 cells having FcRn receptor expression and forming the monolayer-polarized structure. The cellular toxicity of both delivery vehicle and the complex revealed their minimal toxicity comparable with nontoxicity of a commercial transfection reagent. Biodistribution of the complex showed the detectable distribution of the complex in the most parts of gastrointestinal tract due to ubiquitous expression of the FcRn receptors. An in vivo type 2 diabetes treatment study of oral administration of hIgG1-Fc-9Arg/pGLP-1 complexes showed absorption and expression in GI tract of either Balb/c mice or Lepdb/db mice.ConclusionIn this study, we developed an oral GLP-1 gene delivery system on the platform of cationic hIgG1-Fc-9Arg. Prolonged t1/2, less immunoactivity, and better bioactivities of hIgG-Fc-9Arg/pGLP-1 complexes appeared to be a promising approach to achieve potent treatment of type 2 diabetes treatment.Electronic supplementary materialThe online version of this article (10.1186/s40824-018-0129-7) contains supplementary material, which is available to authorized users.

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Challenges in Oral Peptide delivery: Lessons Learnt From the Clinic and Future Prospects

Richard

2017

Ther. Deliv.

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Therapeutic peptides have become very successful drugs due to their specificity, potency and low toxicity, but they show challenges for their delivery, due to their short half-life and rapid plasma clearance. For these reasons, peptides are usually administered using injectable sustained-release formulations. Oral peptide route is highly compelling from a patient and commercial point of view. However, poor peptide stability and low permeability across the intestinal epithelium still make it very challenging to effectively deliver peptides by the oral route. In this paper, biopharmaceutical and formulation features of oral peptides, as well as key clinical outcomes, are reviewed and discussed in the perspective of designing next generation of oral peptide formulations for a true paradigm shift.

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Oral nanoparticles

Cited by 3 publications

References 5 publications

In situ self-assembly of peptides in glucan particles for macrophage-targeted oral delivery

In situ self-assembly of peptides in glucan particles for macrophage-targeted oral delivery

Antibody-mediated oral delivery of therapeutic DNA for type 2 diabetes mellitus

Challenges in Oral Peptide delivery: Lessons Learnt From the Clinic and Future Prospects

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