ArticlePharmaceutical research2017
Structure-Function Analysis of Phenylpiperazine Derivatives as Intestinal Permeation Enhancers.
Article in Pharmaceutical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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
11 citing papers in PubMed, 22 citations in OpenAlex.
- Conformational Preferences and Benchmarking of Computational Methods for Piperazine-Based Ligands.ACS omega · 2026Article
- Nanostructure-Mediated Transport of Therapeutics through Epithelial Barriers.International journal of molecular sciences · 2024Review
- Oral Absorption of Middle-to-Large Molecules and Its Improvement, with a Focus on New Modality Drugs.Pharmaceutics · 2023Review
- Sweet Cherry Extract as Permeation Enhancer of Tyrosine Kinase Inhibitors: A Promising Prospective for Future Oral Anticancer Therapies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Storming the gate: New approaches for targeting the dynamic tight junction for improved drug delivery.Advanced drug delivery reviews · 2023Review
- Long-term daily oral administration of intestinal permeation enhancers is safe and effective in mice.Bioengineering & translational medicine · 2023Article
- The strawberry-derived permeation enhancer pelargonidin enables oral protein delivery.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Oral delivery of peptide therapeutics in infants: Challenges and opportunities.Advanced drug delivery reviews · 2021Review
- Investigations of Piperazine Derivatives as Intestinal Permeation Enhancers in Isolated Rat Intestinal Tissue Mucosae.The AAPS journal · 2020Article
- Anionic nanoparticles enable the oral delivery of proteins by enhancing intestinal permeability.Nature biomedical engineering · 2020Article
- Thrifty, Rapid Intestinal Monolayers (TRIM) Using Caco-2 Epithelial Cells for Oral Drug Delivery Experiments.Pharmaceutical research · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeA major obstacle preventing oral administration of macromolecular therapeutics is poor absorption across the intestinal epithelium into the bloodstream. One strategy to improve transport across this barrier is the use of chemical permeation enhancers. Several molecular families with permeation enhancing potential have been identified previously, including piperazines. In particular, 1-phenylpiperazine has been shown to enhance transepithelial transport with minimal cytotoxicity compared to similarly effective molecules. To better understand how the chemistry of 1-phenylpiperazine affects its utility as an intestinal permeation enhancer, this study examined a small library of 13 derivatives of 1-phenylpiperazine.
methodsThe efficacy and cytotoxicity of 13 phenylpiperazine compounds were assessed in a Caco-2 model of the intestinal epithelium. Efficacy was measured using the paracellular diffusion marker calcein as well as by immunostaining and confocal imaging of Caco-2 monolayers.
resultsOf the 13 derivatives, two enhanced the permeability of the fluorescent marker calcein over 100-fold. It was found that hydroxyl or primary amine substitutions on the phenyl ring significantly increased toxicity, while aliphatic substitutions resulted in efficacy and toxicity profiles comparable to 1-phenylpiperazine.
conclusionsSeveral potent derivatives, including 1-methyl-4-phenylpiperazine and 1-(4-methylphenyl)piperazine, displayed lower toxicity than 1-phenylpiperazine, suggesting promise in future applications.
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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.