| Title |
An Assessment of the Permeation Enhancer, 1-phenyl-piperazine (PPZ), on Paracellular Flux Across Rat Intestinal Mucosae in Ussing Chambers
|
|---|---|
| Published in |
Pharmaceutical Research, July 2016
|
| DOI | 10.1007/s11095-016-1975-4 |
| Pubmed ID | |
| Authors |
V. A. Bzik, D. J. Brayden |
| Abstract |
1-phenyl piperazine (PPZ) emerged from a Caco-2 monolayer screen as having high enhancement potential due to a capacity to increase permeation without significant toxicity. Our aim was to further explore the efficacy and toxicity of PPZ in rat ileal and colonic mucosae in order to assess its true translation potential. Intestinal mucosae were mounted in Ussing chambers and apparent permeability coefficient (Papp) values of [(14)C]-mannitol and FITC-dextran 4 kDa (FD-4) and transepithelial electrical resistance (TEER) values were obtained following apical addition of PPZ (0.6-60 mM). Exposed issues were assessed for toxicity by histopathology and lactate dehydrogenase (LDH) release. Mucosal recovery after exposure was also assessed using TEER readings. PPZ reversibly increased the Papp of both agents across rat ileal and distal colonic mucosae in concentration-dependent fashion, accompanied by TEER reduction, with acceptable levels of tissue damage. The complex mechanism of tight junction opening was part mediated by myosin light chain kinase, stimulation of transepithelial electrogenic chloride secretion, and involved activation of 5-HT4 receptors. PPZ is an efficacious and benign intestinal permeation enhancer in tissue mucosae. However, its active pharmacology suggest that potential for further development in an oral formulation for poorly permeable molecules will be difficult. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Ireland | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| Sweden | 1 | 3% |
| Unknown | 31 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 24% |
| Student > Bachelor | 6 | 18% |
| Student > Master | 4 | 12% |
| Researcher | 4 | 12% |
| Other | 2 | 6% |
| Other | 1 | 3% |
| Unknown | 8 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 15% |
| Agricultural and Biological Sciences | 4 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 9% |
| Engineering | 3 | 9% |
| Medicine and Dentistry | 3 | 9% |
| Other | 5 | 15% |
| Unknown | 10 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 September 2016.
All research outputs
#20,721,996
of 23,321,213 outputs
Outputs from Pharmaceutical Research
#2,672
of 2,888 outputs
Outputs of similar age
#310,666
of 357,095 outputs
Outputs of similar age from Pharmaceutical Research
#42
of 46 outputs
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