A Novel Design of Artificial Membrane for Improving the PAMPA Model

Chen, Xiaoxi; Murawski, Anthony; Patel, Karishma; Crespi, Charles L.; Balimane, Praveen

doi:10.1007/s11095-007-9517-8

Cited by 219 publications

(235 citation statements)

References 21 publications

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“…A 96-well donor and accepter plate system pre-loaded with artificial lipid membrane (BD Gentest TM Pre-coated PAMPA Plate) was used. In these plates, each well consists of a polyvinylidene fluoride (PVDF) filter coated with a lipid/oil/lipid trilayer, where the lipid layer is composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine and the oil layer is composed of hexadecane [17]. Acceptor and donor well concentrations were measured using an UHPLC/MS system equipped with a C18 Kinetex (2.10 x 50 mm, 7 μm).…”

Section: Hplcmentioning

confidence: 99%

Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability

Wang

Northfield

Swedberg

et al. 2015

European Journal of Medicinal Chemistry

108

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An increasing number of macrocyclic peptides that cross biological membranes are being reported, suggesting that it might be possible to develop peptides into orally bioavailable therapeutics; however, current understanding of what makes macrocyclic peptides cell permeable is still limited. Here, we synthesized 62 cyclic hexapeptides and characterized their permeability using in vitro assays commonly used to predict in vivo absorption rates, i.e. the Caco-2 and PAMPA assays. We correlated permeability with experimentally measured parameters of peptide conformation obtained using rapid methods based on chromatography and nuclear magnetic resonance spectroscopy. Based on these correlations, we propose a model describing the interplay between peptide permeability, lipophilicity and hydrogen bonding potential. Specifically, peptides with very high permeability have high lipophilicity and few solvent hydrogen bond interactions, whereas peptides with very low permeability have low lipophilicity or many solvent interactions. Our model is supported by molecular dynamics simulations of the cyclic peptides calculated in explicit solvent, providing a structural basis for the observed correlations. This prospective exploration into biomarkers of peptide permeability has the potential to unlock wider opportunities for development of peptides into drugs.3

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Section: Hplcmentioning

confidence: 99%

Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability

Wang

Northfield

Swedberg

et al. 2015

European Journal of Medicinal Chemistry

108

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“…PAMPA models with different lipid compositions have been established; for instance models may consist of a single lipid such as lecithin (Kansy et al, 1998) or mixtures of phosphatidyl-choline, -ethanolamine, -serine, -inositol and cholesterol (biomimetic PAMPA, Sugano et al, 2003). A 20% dodecane solution of a phospholipid mixture (Avdeef et al, 2005), silicone oil and isopropyl myristate (Ottaviani et al, 2006) -which does not occur in vivo -systems of lipid bilayers (Nirasay et al, 2011), and also lipid triple-layers (Chen et al, 2008b) as well as synthetically generated amphiphilic phospholipids (Yu et al, 2015) also exist. An interesting example of a comparison between cell-based and artificial membrane assays was published by Kerns et al (2004), where permeability data from Caco-2 cell monolayer and PAMPA methods was compared.…”

Section: Co-culture and Pathophysiological Modelsmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

124

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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“…The artificial membrane immobilized on a filter is placed between a donor and acceptor compartments (22). Recent studies have described numerous tissuespecific methods that predict the gastrointestinal absorption (23)(24)(25)(26), the penetration through the blood-brain barrier (27)(28)(29) or the barrier function of human skin (30). Our results revealed that modified PAMAM dendrimer with TAT peptide has more capability in the transition of the DNA plasmid through the artificial membrane, as the highest expression of the H5 gene was observed from the delivery system of TAT-conjugated dendrimer compared to the native dendrimer.…”

Section: Discussionmentioning

confidence: 99%

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery

et al. 2016

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-PURPOSE:In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. METHODS: First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TATconjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. RESULTS: TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-). In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine. The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (P<0.05). CONCLUSIONS: The findings of this study suggest that TAT-conjugated PAMAM dendrimer is a promising non-viral vector for transdermal use.

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A Novel Design of Artificial Membrane for Improving the PAMPA Model

Abstract: The new artificial membrane provides an improved PAMPA model.

Cited by 219 publications

References 21 publications

Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability

Exploring experimental and computational markers of cyclic peptides: Charting islands of permeability

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery

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