scholarly journals Predicting A Drug'S Membrane Permeability: Evolution of a Computational Model Validated with in Vitro Permeability Assay Data

2016 ◽  
Vol 110 (3) ◽  
pp. 330a ◽  
Author(s):  
Timothy S. Carpenter ◽  
M. Windy McNerney ◽  
Nicholas A. Be ◽  
Victoria Lao ◽  
Emma M. Carlson ◽  
...  
Keyword(s):  
Computational Model ◽  
Membrane Permeability ◽  
Permeability Evolution ◽  
Permeability Assay

scholarly journals Predicting a Drug’s Membrane Permeability: A Computational Model Validated With in Vitro Permeability Assay Data

2017 ◽  
Vol 121 (20) ◽  
pp. 5228-5237 ◽  
Author(s):  
Brian J. Bennion ◽  
Nicholas A. Be ◽  
M. Windy McNerney ◽  
Victoria Lao ◽  
Emma M. Carlson ◽  
...  
Keyword(s):  
Computational Model ◽  
Membrane Permeability ◽  
Permeability Assay

scholarly journals Paraben Transport and Metabolism in the Biomimetic Artificial Membrane Permeability Assay (BAMPA) and 3-Day and 21-Day Caco-2 Cell Systems

2006 ◽  
Vol 12 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Mark Lakeram ◽  
David J. Lockley ◽  
David J. Sanders ◽  
Ruth Pendlington ◽  
Ben Forbes
Keyword(s):  
Membrane Permeability ◽  
Systemic Exposure ◽  
In Vitro Models ◽  
Log P ◽  
Hydroxybenzoic Acid ◽  
Artificial Membrane ◽  
Parabolic Relationship ◽  
Permeability Assay

Noncellular and cellular in vitro models for predicting intestinal absorption were used to investigate the transport and metabolism of parabens. The biomimetic artificial membrane permeability assay (BAMPA) membrane was constructed by impregnating a lipid solution on a hydrophobic filter. Caco-2 cells at passage numbers 65 to 80 were cultured in either the accelerated 3-day Biocoat™ system or the standard 21-day Transwell™ cell culture system. Paraben transport across the BAMPA system showed a parabolic relationship. The lowest log P (p-hydroxybenzoic acid) and highest log P compounds (heptyl and octyl parabens) had apparent permeabilities (Papp) less than 1.0 × 10-6 cm/s and Papp was maximal at approximately 8.5 × 10-6cm/s for the intermediate log P (ethylparaben) compound. With the Biocoat™, a similar parabolic relationship was found. In the 21-day Caco-2 cells, the parabens were metabolized by esterases at to p-hydroxybenzoic acid. In conclusion, the in vitro models added complementary insight into the absorption process, such as the transport route, intrinsic permeability, and extent of metabolism of the parabens. This study indicated that presystemic metabolism of orally ingested parabens to the p-hydroxybenzoic acid in the intestine may limit systemic exposure to alkyl-paraben esters in vivo.

scholarly journals Prediction of Permeation and Cellular Transport of Silybum marianum Extract Formulated in a Nanoemulsion by Using PAMPA and Caco-2 Cell Models

Planta Medica ◽  
2017 ◽  
Vol 83 (14/15) ◽  
pp. 1184-1193 ◽  
Author(s):  
Vieri Piazzini ◽  
Chiara Rosseti ◽  
Elisabetta Bigagli ◽  
Cristina Luceri ◽  
Anna Bilia ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Oral Delivery ◽  
Oral Absorption ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Cellular Transport ◽  
Artificial Membrane ◽  
Silybum Marianum ◽  
Permeability Assay

AbstractThe present study explores the potential of nanoemulsion, a lipid drug delivery system, to improve solubility and oral absorption of Silybum marianum extract. The optimized formulation contained 40 mg/mL of commercial extract (4 % w/w) and it was composed of 2.5 g labrasol (20 %) as the oil phase, 1.5 g cremophor EL as the surfactant, and 1 g labrafil as the cosurfactant (mixture surfactant/cosurfactant, 20 %).The system was characterized by dynamic light scattering, transmission electron microscopy, and HPLC-DAD analyses in order to evaluate size, homogeneity, morphology, and encapsulation efficiency. Physical and chemical stabilities were assessed during 40 days at 4 °C and 3 months at 25 °C. Stability in simulated gastric fluid followed by simulated intestinal conditions was also considered. In vitro permeation studies were performed to determine the suitability of the prepared nanoemulsion for oral delivery. Different models such as the parallel artificial membrane permeability assay and Caco-2 cell lines were applied.The nanoemulsion showed a good solubilizing effect of the extract, with a pronounced action also on its permeability, in respect to a saturated aqueous solution. The Caco-2 test confirmed the parallel artificial membrane permeability assay results and they revealed the suitability of the prepared nanoemulsion for oral delivery.

scholarly journals PenA, a penicillin-binding protein-type thioesterase specialized for small peptide cyclization

2021 ◽  
Author(s):  
Kenichi Matsuda ◽  
Kei Fujita ◽  
Toshiyuki Wakimoto
Keyword(s):  
Enzymatic Activity ◽  
Computational Model ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Small Peptide ◽  
Peptide Cyclization ◽  
Chain Lengths ◽  
Non Ribosomal Peptides

Abstract Penicillin binding protein-type thioesterases (PBP-type TEs) are a recently identified group of peptide cyclases that catalyze head-to-tail macrolactamization of non-ribosomal peptides. PenA, a new member of this group, is involved in the biosyntheses of cyclic pentapeptides. In this study, we demonstrated the enzymatic activity of PenA in vitro, and analyzed its substrate scope with a series of synthetic substrates. A comparison of the reaction profiles between PenA and SurE, a representative PBP-type TE, showed that PenA is more specialized for small peptide cyclization. A computational model provided a possible structural rationale for the altered specificity for substrate chain lengths.

scholarly journals Modelling human skull growth: a validated computational model

2017 ◽  
Vol 14 (130) ◽  
pp. 20170202 ◽  
Author(s):  
Joseph Libby ◽  
Arsalan Marghoub ◽  
David Johnson ◽  
Roman H. Khonsari ◽  
Michael J. Fagan ◽  
...  
Keyword(s):  
Computational Model ◽  
Three Dimensional ◽  
Basic Knowledge ◽  
Fe Model ◽  
Adult Size ◽  
Fe Method ◽  
Percentage Difference ◽  
Skull Growth

During the first year of life, the brain grows rapidly and the neurocranium increases to about 65% of its adult size. Our understanding of the relationship between the biomechanical forces, especially from the growing brain, the craniofacial soft tissue structures and the individual bone plates of the skull vault is still limited. This basic knowledge could help in the future planning of craniofacial surgical operations. The aim of this study was to develop a validated computational model of skull growth, based on the finite-element (FE) method, to help understand the biomechanics of skull growth. To do this, a two-step validation study was carried out. First, an in vitro physical three-dimensional printed model and an in silico FE model were created from the same micro-CT scan of an infant skull and loaded with forces from the growing brain from zero to two months of age. The results from the in vitro model validated the FE model before it was further developed to expand from 0 to 12 months of age. This second FE model was compared directly with in vivo clinical CT scans of infants without craniofacial conditions ( n = 56). The various models were compared in terms of predicted skull width, length and circumference, while the overall shape was quantified using three-dimensional distance plots. Statistical analysis yielded no significant differences between the male skull models. All size measurements from the FE model versus the in vitro physical model were within 5%, with one exception showing a 7.6% difference. The FE model and in vivo data also correlated well, with the largest percentage difference in size being 8.3%. Overall, the FE model results matched well with both the in vitro and in vivo data. With further development and model refinement, this modelling method could be used to assist in preoperative planning of craniofacial surgery procedures and could help to reduce reoperation rates.

scholarly journals Metabolism of Selected 2-Arylbenzofurans in a Colon In Vitro Model System

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2754
Author(s):  
Ondrej Vesely ◽  
Petr Marsik ◽  
Veronika Jarosova ◽  
Ivo Doskocil ◽  
Karel Smejkal ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Biological Effects ◽  
Bacterial Fermentation ◽  
Basolateral Side ◽  
Sufficient Stability ◽  
Polar Metabolites ◽  
Fermentation Model ◽  
Vitro Model ◽  
Permeability Assay

2-arylbenzofurans represent a small group of bioactive compounds found in the plant family Moraceae. As it has not been investigated whether these substances are stable during passage through the gastrointestinal tract, their biological effects may be altered by the metabolism of intestinal microbiota or cells. The aim of the present study was to investigate and compare mulberrofuran Y (1), moracin C (2), and mulberrofuran G (3) in an in vitro model of human intestinal bacterial fermentation and in an epithelial model using the Caco-2 cell line. The analysis of compounds by LC-MS-Q-TOF showed sufficient stability in the fermentation model, with no bacterial metabolites detected. However, great differences in the quantity of permeation were observed in the permeability assay. Moreover, mulberrofuran Y (1) and moracin C (2) were observed to be transformed into polar metabolites by conjugation. Among the test compounds, mulberrofuran Y (1) was mostly stable and accumulated in endothelial cells (85.3%) compared with mulberrofuran G (3) and moracin C (2) (14% and 8.2%, respectively). Thus, only a small amount of mulberrofuran Y (1) was conjugated. Moracin C (2) and mulberrofuran G (3) were metabolized almost completely, with only traces of the unchanged molecule being found on the apical and cellular sides of the system. Only conjugates of mulberrofuran Y (1) and moracin C (2) were able to reach the basolateral side. Our results provide the basic description of bioavailability of these three compounds, which is a necessary characteristic for final evaluation of bio-efficacy.

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