ArticlePharmaceutical research1997
Effect of size and charge on the passive diffusion of peptides across Caco-2 cell monolayers via the paracellular pathway.
Article in Pharmaceutical research, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- Overall Evidence for Milk-Derived Proteins and Peptides in Blood after Digestion: A Systematic Review.Nutrition reviews · 2025Pooled it
- Design of self-emulsifying oral delivery systems for semaglutide: reverse micelles versus hydrophobic ion pairs.Drug delivery and translational research · 2025Article
- LAP-Hsp60 complex modulates epithelial tight junction barrier.Research square · 2025Article
- Molecular Modelling in Bioactive Peptide Discovery and Characterisation.Biomolecules · 2025Review
- Improving the Accuracy of Permeability Data to Gain Predictive Power: Assessing Sources of Variability in Assays Using Cell Monolayers.Membranes · 2024Review
- Current Evidence on the Bioavailability of Food Bioactive Peptides.Molecules (Basel, Switzerland) · 2020Review
- The dynamic process of dietary soybean β-conglycinin in digestion, absorption, and metabolism among different intestinal segments in grass carp (Ctenopharyngodon idella).Fish physiology and biochemistry · 2020Article
- In Silico Prediction of Intestinal Permeability by Hierarchical Support Vector Regression.International journal of molecular sciences · 2020Article
- Mechanistic Studies on the Absorption-Enhancing Effects of Gemini Surfactant on the Intestinal Absorption of Poorly Absorbed Hydrophilic Drugs in Rats.Pharmaceutics · 2019Article
- Strategies to Enhance Drug Absorption via Nasal and Pulmonary Routes.Pharmaceutics · 2019Review
- Novel self-nanomicellizing solid dispersion based on rebaudioside A: a potential nanoplatform for oral delivery of curcumin.International journal of nanomedicine · 2019Article
- Hydrophobicity of Antifungal β-Peptides Is Associated with Their Cytotoxic Effect on In Vitro Human Colon Caco-2 and Liver HepG2 Cells.PloS one · 2016Article
- Sensitivity and mechanisms of taxol-resistant prostate adenocarcinoma cells to Vernonia amygdalina extract.Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie · 2013Article
- Approaches for enhancing oral bioavailability of peptides and proteins.International journal of pharmaceutics · 2013Review
- Getting in shape: controlling peptide bioactivity and bioavailability using conformational constraints.ACS chemical biology · 2013Review
- Lipophilicity and its relationship with passive drug permeation.Pharmaceutical research · 2011Review
- Modeling kinetics of subcellular disposition of chemicals.Chemical reviews · 2009Review
- The role of size and charge for blood-brain barrier permeation of drugs and fatty acids.Journal of molecular neuroscience : MN · 2007Article
- Interplay of secondary structure and charge on the diffusion of a polypeptide through negatively charged aqueous pores.Pharmaceutical research · 2007Article
- Electroaffinity in paracellular absorption of hydrophilic D-dipeptides by sparrow intestine.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo evaluate the effect of size and charge on the permeation characteristics of peptides across the intestinal mucosa.
methodsThe lipophilicities of neutral, positively and negatively charged capped amino acids (Asn, Lys, Asp), tripeptides (Ac-Gly-X-Ala-NH2; X = Asn, Lys, Asp) and hexapeptides (Ac-Trp-Ala-Gly-Gly-X-Ala-NH2; X = Asn, Lys, Asp) were estimated using an immobilized artificial membrane. The diffusion coefficients used to calculate the molecular radii were measured by NMR. The transport characteristics of the model peptides were determined across Caco-2 cell monolayers.
resultsWhen model compounds having the same charge were compared, permeation was highly size-dependent (capped amino acids > tripeptides > hexapeptides), suggesting transport predominantly via the paracellular route. For example, the flux of the negatively charged Asp amino acid (Papp = 10.04 +/- 0.43 x 10(-8) cm/s) was 3 times greater than that observed for the Asp-containing hexapeptide (Papp = 3.19 +/- 0.27 x 10(-8) cm/s). When model compounds of the same size were compared, permeation across the cell monolayer was charge-dependent (negative < positive < or = neutral). For example, the neutral, Asn-containing tripeptide (Papp = 25.79 +/- 4.86 x 10(-8) cm/s) was substantially more able to permeate the Caco-2 cell monolayer than the negatively charged Asp-containing tripeptide (Papp = 7.95 +/- 1.03 x 10(-8) cm/s) and the positively charged Lys-containing tripeptide (Papp = 9.86 +/- 0.18 x 10(-8) cm/s). The permeability of the cell monolayer to peptides became less sensitive to net charge as the size of the peptides increased.
conclusionsA positive net charge of hydrophilic peptides enhances their permeation across the intestinal mucosa via the paracellular pathway. With increasing molecular size, molecular sieving of the epithelial barrier dominates the transport of peptides, and the effect of the net charge becomes less significant.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.