Skin–PAMPA: A new method for fast prediction of skin penetration

Sinkó, Bálint; Garrigues, Teresa María; Balogh, György Tibor; Nagy, Zsombor Kristóf; Tsinman, Oksana; Avdeef, Alex; Takács‐Novák, Krisztina

doi:10.1016/j.ejps.2012.01.011

Cited by 158 publications

(114 citation statements)

References 37 publications

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“…The PAMPA measures the ability of a compound to diffuse from a donor compartment (containing the tested compound diluted in buffer) to an acceptor compartment (containing simply buffer), which are separated by a lipophilic artificial membrane and is performed in a 96-well plate. Depending on the composition of the artificial membrane used, different biological barriers can be mimicked, such as the GIT [11,12], the BBB [13,14], or the dermal layer [15,16]. After the incubation time, the ratio of compound which has crossed the artificial membrane is calculated and used to obtain the effective passive permeability value P e (cm/s), which is a constant value for each compound tested (see Material and Methods for details on the equations).…”

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confidence: 99%

Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

et al. 2016

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At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high-throughput, cost-effective, and early evaluation of passive intestinal absorption of active principles in medicinal plants. In phytochemical studies, obtaining effective passive permeability values of pharmacologically active natural products is important to predict if natural products showing interesting activities in vitro may have a chance to reach their target in vivo.

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confidence: 99%

Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

et al. 2016

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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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“…have studied three artificial membranes isopropyl myristate (IPM), certramides and a new synthetic skin (Strat-M™) using PAMPA for skin (Sinko et al,, 2012). Although the compounds they used were not PAH, they used sodium diclofenac which has similar log Koc and MW (4.5 and 318 respectively) to PAH found in soil samples.…”

Section: In Vitro Membrane Types Usedmentioning

confidence: 99%

“…Using this approach they were able to carry out 6 diffusion cell experiments in parallel. Sinko et al (2012) have developed this further by modifying a 96 well Parallel Artificial Membrane Permeability Assay (PAMPA) (Figure 4) that had already been used for estimating passive gastrointestinal absorption and blood-brain barrier permeability. In a follow up study, used the PAMPA methodology to compare the performance of synthetic skin membranes to porcine skin on a variety of organic compounds.…”

Section: Diffusion Cell Design and Operationmentioning

confidence: 99%

A review of the current state of the art of physiologically-based tests for measuring human dermal in vitro bioavailability of polycyclic aromatic hydrocarbons (PAH) in soil

Beriro

Cave

Wragg

et al. 2016

Journal of Hazardous Materials

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Polycyclic Aromatic Hydrocarbons are classed as Persistent Organic Pollutants, a large group of compounds that share similar characteristics. They are lipophilic, resistant to degradation in the environment and harmful to human and environmental health. Soil has been identified as the primary reservoir for Polycyclic Aromatic Hydrocarbons in the United Kingdom. This study reviews the literature associated with, or is relevant to, the measurement and modelling of dermal absorption of Polycyclic Aromatic Hydrocarbons from soils. The literature illustrates the use of in vivo, in vitro and in silico methods from a wide variety of scientific disciplines including occupational and environmental exposure, medical, pharmaceutical and cosmetic research and associated mathematical modelling. The review identifies a number of practical shortcomings which must be addressed if they are to be applied to high throughput laboratory analysis of contaminated soils for human health risk assessment.

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Skin–PAMPA: A new method for fast prediction of skin penetration

Cited by 158 publications

References 37 publications

Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA)

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery

A review of the current state of the art of physiologically-based tests for measuring human dermal in vitro bioavailability of polycyclic aromatic hydrocarbons (PAH) in soil

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