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1.
Pharm Res ; 41(3): 567-576, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38351229

RESUMO

PURPOSE: This study investigates in silico the contribution of the hair follicle to the overall dermal permeability of small molecules, as published experimental work provides inconclusive information on whether the follicular route favours the permeation of hydrophobic or hydrophilic permeants. METHOD: A study is conducted varying physico-chemical parameters of permeants such as lipophilicity, molecular weight and protein binding. The simulated data is compared to published experimental data to discuss how those properties can modulate the contribution of the hair follicle to the overall dermal permeation. RESULTS: The results indicate that the contribution of the follicular route to dermal permeation can range from negligible to notable depending on the combination of lipophilic/hydrophilic properties of the substance filling the follicular route and the permeant. CONCLUSION: Characterisation of the substance filling the follicular route is required for analysing the experimental data of dermal permeation of small molecules, as changes between in vivo and in vitro due to handling of samples and cessation of vital functions can modify the contribution of the follicular route to overall dermal permeation, hence hindering data interpretation.


Assuntos
Folículo Piloso , Absorção Cutânea , Folículo Piloso/metabolismo , Permeabilidade , Interações Hidrofóbicas e Hidrofílicas , Pele/metabolismo
2.
Toxicol Mech Methods ; 34(2): 164-175, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37794615

RESUMO

Comprehensive analysis of multi-omics data can reveal alterations in regulatory pathways induced by cellular exposure to chemicals by characterizing biological processes at the molecular level. Data-driven omics analysis, conducted in a dose-dependent or dynamic manner, can facilitate comprehending toxicity mechanisms. This study introduces a novel multi-omics data analysis designed to concurrently examine dose-dependent and temporal patterns of cellular responses to chemical perturbations. This analysis, encompassing preliminary exploration, pattern deconstruction, and network reconstruction of multi-omics data, provides a comprehensive perspective on the dynamic behaviors of cells exposed to varying levels of chemical stimuli. Importantly, this analysis is adaptable to any number of omics layers, including site-specific phosphoproteomics. We implemented this analysis on multi-omics data obtained from HepG2 cells exposed to a range of caffeine doses over varying durations and identified six response patterns, along with their associated biomolecules and pathways. Our study demonstrates the effectiveness of the proposed multi-omics data analysis in capturing multidimensional patterns of cellular response to chemical perturbation, enhancing understanding of pathway regulation for chemical risk assessment.


Assuntos
Cafeína , Genômica , Genômica/métodos , Cafeína/toxicidade , Multiômica , Análise de Dados
3.
Toxicol In Vitro ; 93: 105702, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37769857

RESUMO

Permeability and partition coefficients of the skin barrier are important for assessing dermal absorption, bioavailability, and safety of cosmetics and medicine. We use the Potts and Guy equation to analyse the dependence of skin permeability on the hydrophobicity of permeants and highlight the significant differences in published datasets. Correlations of solute partition to skin are examined to understand the likely causes of the differences in the skin permeability datasets. Recently published permeability datasets show weak correlation and low dependence on hydrophobicity. As expected, early datasets show good correlation with hydrophobicity due to the related derivation. The weaker correlation of later datasets cannot be explained by the partition to skin lipids. All the datasets of solute partition to skin lipid showed a similar correlation to hydrophobicity where the log-linear correlation coefficient of partition is almost the same of the log-linear coefficient of Potts and Guy equation. Weak correlation and dependence of the late permeability datasets with SC lipid/water partition and that they are significantly under predicted by the Potts and Guy equation suggests either additional non-lipid pathway at play or a weaker skin barrier property.


Assuntos
Absorção Cutânea , Pele , Masculino , Humanos , Pele/metabolismo , Permeabilidade , Interações Hidrofóbicas e Hidrofílicas , Lipídeos
4.
J Phys Chem B ; 127(12): 2719-2728, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36930176

RESUMO

Stratum corneum (SC) is the main barrier of human skin where the inter-corneocytes lipids provide the main pathway for transdermal permeation of functional actives of skin care and health. Molecular dynamics (MD) has been increasingly used to simulate the SC lipid bilayer structure so that the barrier property and its affecting factors can be elucidated. Among reported MD simulation studies, solute partition in the SC lipids, an important parameter affecting SC permeability, has received limited attention. In this work, we combine MD simulation with COSMOmic to predict the partition coefficients of dermatologically relevant solutes in SC lipid bilayer. Firstly, we run MD simulations to obtain equilibrated SC lipid bilayers with different lipid types, compositions, and structures. Then, the simulated SC lipid bilayer structures are fed to COSMOmic to calculate the partition coefficients of the solutes. The results show that lipid types and bilayer geometries play a minor role in the predicted partition coefficients. For the more lipophilic solutes, the predicted results of solute partition in SC lipid bilayers agree well with reported experimental values of solute partition in extracted SC lipids. For the more hydrophilic molecules, there is a systematical underprediction. Nevertheless, the MD/COSMOmic approach correctly reproduces the phenomenological correlation between the SC lipid/water partition coefficients and the octanol/water partition coefficients. Overall, the results show that the MD/COSMOmic approach is a fast and valid method for predicting solute partitioning into SC lipids and hence supporting the assessment of percutaneous absorption of skin care ingredients, dermatological drugs as well as environmental pollutants.


Assuntos
Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Humanos , Bicamadas Lipídicas/química , Pele/metabolismo , Epiderme/metabolismo , Água/química
5.
J Appl Toxicol ; 43(6): 940-950, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609694

RESUMO

In silico methods to estimate and/or quantify skin absorption of chemicals as a function of chemistry are needed to realistically predict pharmacological, occupational, and environmental exposures. The Potts-Guy equation is a well-established approach, using multi-linear regression analysis describing skin permeability (Kp) in terms of the octanol/water partition coefficient (logP) and molecular weight (MW). In this work, we obtained regression equations for different human datasets relevant to environmental and cosmetic chemicals. Since the Potts-Guy equation was published in 1992, we explored recent datasets that include different skin layers, such as dermatomed (including dermis to a defined thickness) and full skin. Our work was consistent with others who have observed that fits to the Potts-Guy equation are stronger for experiments focused on the epidermis. Permeability estimates for dermatomed skin and full skin resulted in low regression coefficients when compared to epidermis datasets. An updated regression equation uses a combination of fitted permeability values obtained with a published 2D compartmental model previously evaluated. The resulting regression equation was: logKp = -2.55 + 0.65logP - 0.0085MW, R2 = 0.91 (applicability domain for all datasets: MW ranges from 18 to >584 g/mol and -4 to >5 for logP). This approach demonstrates the advantage of combining mechanistic with structural activity relationships in a single modeling approach. This combination approach results in an improved regression fit when compared to permeability estimates obtained using the Potts-Guy approach alone. The analysis presented in this work assumes a one-compartment skin absorption route; future modeling work will consider adding multiple compartments.


Assuntos
Absorção Cutânea , Pele , Masculino , Humanos , Pele/metabolismo , Análise de Regressão , Modelos Lineares , Permeabilidade
6.
Pharm Res ; 40(1): 295-305, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36348132

RESUMO

OBJECTIVES: To develop a simulation model to explore the interplay between mechanical stretch and diffusion of large molecules into the skin under locally applied hypobaric pressure, a novel penetration enhancement method. METHODS: Finite element method was used to model the skin mechanical deformation and molecular diffusion processes, with validation against in-vitro transdermal permeation experiments. Simulations and experimental data were used together to investigate the transdermal permeation of large molecules under local hypobaric pressure. RESULTS: Mechanical simulations resulted in skin stretching and thinning (20%-26% hair follicle diameter increase, and 21%-27% skin thickness reduction). Concentration of dextrans in the stratum corneum was below detection limit with and without hypobaric pressure. Concentrations in viable epidermis and dermis were not affected by hypobaric pressure (approximately 2 µg [Formula: see text] cm-2). Permeation into the receptor fluid was substantially enhanced from below the detection limit at atmospheric pressure to up to 6 µg [Formula: see text] cm-2 under hypobaric pressure. The in-silico simulations compared satisfactorily with the experimental results at atmospheric conditions. Under hypobaric pressure, satisfactory comparison was attained when the diffusion coefficients of dextrans in the skin layers were increased from [Formula: see text] 10 µm2 [Formula: see text] s-1 to between 200-500 µm2 [Formula: see text] s-1. CONCLUSIONS: Application of hypobaric pressure induces skin mechanical stretching and enlarges the hair follicle. This enlargement alone cannot satisfactorily explain the increased transdermal permeation into the receptor fluid under hypobaric pressure. The results from the in-silico simulations suggest that the application of hypobaric pressure increases diffusion in the skin, which leads to improved overall transdermal permeation.


Assuntos
Dextranos , Pele , Preparações Farmacêuticas , Administração Cutânea , Epiderme
7.
J Chem Inf Model ; 61(7): 3376-3385, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34161083

RESUMO

Liquid-liquid extraction (LLE) is an important technique to separate aromatics from aliphatics since these compounds have very similar boiling points and cannot be separated by distillation. Ionic liquids (ILs) are considered as potential extractants to extract aromatics from aliphatics. In this paper, molecular dynamics (MD) simulations were used to predict the extraction property (i.e., capacity and selectivity) of ILs for the LLE of aromatics from aliphatics. The extraction properties of seven different ILs including [C2mim][Tf2N], [C2mim][TFO], [C2mim][SCN], [C2mim][DCA], [C2mim][TCM], [C4mim][Tf2N], and [C8mim][Tf2N] were investigated. Results show that ILs with shorter alkyl chain cations and [Tf2N]- anion exhibit better extraction efficiency than other ILs, which is in agreement with previously reported experimental data on the extraction of toluene from aliphatics and further validated the reliability of the proposed model. The binding energies between ILs and organic molecules were calculated by the density functional theory, which help explain the different extraction behaviors of different ILs. The symmetry-adapted perturbation theory analysis was performed to further understand the interaction mechanisms between ILs and organics. Our study shows that the [Tf2N]- anion also has the best extraction capability for heavier aromatics (o-xylene, m-xylene, and p-xylene) from common aliphatics (heptane and octane). The MD modeling approach can be a low-cost in silico tool for the high-throughput fast screening of ILs for the LLE of aromatics from aliphatics.


Assuntos
Líquidos Iônicos , Ânions , Extração Líquido-Líquido , Simulação de Dinâmica Molecular , Reprodutibilidade dos Testes
8.
Food Funct ; 12(12): 5399-5406, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-33988204

RESUMO

Inhibition of glucose uptake in the intestine through sodium-dependent glucose transporter 1 (SGLT1) or glucose transporter 2 (GLUT2) may be beneficial in controlling postprandial blood glucose levels. Gallic acid and ten of its derivatives were identified in the active fractions of Terminalia chebula Retz. fructus immaturus, a popular edible plant fruit which has previously been associated with the inhibition of glucose uptake. Gallic acid derivatives (methyl gallate, ethyl gallate, pentyl gallate, 3,4,6-tri-O-galloyl-ß-d-glucose, and corilagin) showed good glucose transport inhibition with inhibitory rates of 72.1 ± 1.6%, 71.5 ± 1.4%, 79.9 ± 1.2%, 44.7 ± 1.2%, and 75.0 ± 0.7% at 5 mM d-glucose and/or 56.3 ± 2.3, 52.1 ± 3.2%, 70.2 ± 1.7%, 15.6 ± 1.6%, and 37.1 ± 0.8% at 25 mM d-glucose. However, only 3,4,6-tri-O-galloyl-ß-d-glucose and corilagin were confirmed GLUT2-specific inhibitors. Whilst some tea flavonoids demonstrated minimal glucose transport inhibition, their gallic acid derivatives strongly inhibited transport effect with GLUT2 specificity. This suggests that gallic acid structures are crucial for glucose transport inhibition. Plants, such as T. chebula, which contain high levels of gallic acid and its derivatives, show promise as natural functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels.


Assuntos
Transporte Biológico/efeitos dos fármacos , Ácido Gálico/química , Ácido Gálico/farmacologia , Glucose/metabolismo , Extratos Vegetais/farmacologia , Período Pós-Prandial/efeitos dos fármacos , Células CACO-2 , Flavonoides , Frutas/química , Ácido Gálico/análogos & derivados , Transportador de Glucose Tipo 2 , Glucosídeos , Humanos , Taninos Hidrolisáveis , Intestinos , Transportador 1 de Glucose-Sódio , Terminalia/efeitos dos fármacos
9.
Skin Res Technol ; 27(5): 948-958, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33822382

RESUMO

BACKGROUND: Suction cups are widely used in applications such as in measurement of mechanical properties of skin in vivo, in drug delivery devices or in acupuncture treatment. Understanding mechanical response of skin under hypobaric pressure is of great importance for users of suction cups. The aim of this work is to predict the hypobaric pressure induced 3D stretching of the skin. METHODS: Experimental skin tensile tests were carried out for mechanical property characterization. Both linear elasticity and hyperelasticity parameters were determined and implemented in Finite Element modelling. Skin suction tests were performed in both experiments and FEM simulations for model validation. 3D skin stretching is then visualized in detail in FEM simulations. RESULTS: The simulations showed that the skin was compressed consistently along the thickness direction, leading to reduced thickness. At the center of the dome, the radial and angular strain decreases from the top surface to the bottom surface, although always in tension. Hyperelasticity modelling showed superiority over linear elasticity modelling while predicting the strain distribution because the stretch ratio reaches values exceeding the initial linear elastic stage of the stress-strain curve for skin. CONCLUSION: Hyperelasticity modelling is an effective approach to predict the 3D strain distribution, which paves a way to accurately design safe commercial products that interface with the skin.


Assuntos
Pele , Fenômenos Biomecânicos , Elasticidade , Análise de Elementos Finitos , Pressão , Estresse Mecânico
10.
ACS Omega ; 6(51): 35363-35374, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34984268

RESUMO

Recently, molecular dynamics (MD) simulations have been utilized to investigate the barrier properties of human skin stratum corneum (SC) lipid bilayers. Different MD methods and force fields have been utilized, with predicted permeabilities varying by few orders of magnitude. In this work, we compare constrained MD simulations with restrained MD simulations to obtain the potential of the mean force and the diffusion coefficient profile for the case of a water molecule permeating across an SC lipid bilayer. Corresponding permeabilities of the simulated lipid bilayer are calculated via the inhomogeneous solubility diffusion model. Results show that both methods perform similarly, but restrained MD simulations have proven to be the more robust approach for predicting the potential of the mean force profile. Critical to both methods are the sampling of the whole trans-bilayer axis and the following symmetrization process. Re-analysis of the previously reported free energy profiles showed that some of the discrepancies in the reported permeability values is due to misquotation of units, while some are due to the inaccurately obtained potential of the mean force. By using the existing microscopic geometrical models via the intercellular lipid pathway, the permeation through the whole SC is predicted from the MD simulation results, and the predicted barrier properties have been compared to experimental data from the literature with good agreement.

11.
Pharm Res ; 37(12): 241, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175239

RESUMO

PURPOSE: To advance physiologically-based pharmacokinetic modelling of xenobiotic metabolism by integrating metabolic kinetics with percutaneous absorption. METHOD: Kinetic rate equations were proposed to describe the metabolism of a network of reaction pathways following topical exposure and incorporated into the diffusion-partition equations of both xenobiotics and metabolites. The published ex vivo case study of aromatic amines was simulated. Diffusion and partition properties of xenobiotics and subsequent metabolites were determined using physiologically-based quantitative structure property relationships. Kinetic parameters of metabolic reactions were best fitted from published experimental data. RESULTS: For aromatic amines, the integrated transdermal permeation and metabolism model produced data closely matched by experimental results following limited parameter fitting of metabolism rate constants and vehicle:water partition coefficients. The simulation was able to produce dynamic concentration data for all the dermal layers, as well as the vehicle and receptor fluid. CONCLUSION: This mechanistic model advances the dermal in silico functionality. It provides improved quantitative spatial and temporal insight into exposure of xenobiotics, enabling the isolation of governing features of skin. It contributes to accurate modelling of concentrations of xenobiotics reaching systemic circulation and additional metabolite concentrations. This is vital for development of both pharmaceuticals and cosmetics.


Assuntos
Aminas/farmacocinética , Simulação por Computador , Modelos Biológicos , Absorção Cutânea , Pele/metabolismo , Xenobióticos/farmacocinética , Administração Cutânea , Aminas/administração & dosagem , Disponibilidade Biológica , Difusão , Humanos , Xenobióticos/administração & dosagem
12.
Front Plant Sci ; 11: 510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508853

RESUMO

The utilization of machine vision and its associated algorithms improves the efficiency, functionality, intelligence, and remote interactivity of harvesting robots in complex agricultural environments. Machine vision and its associated emerging technology promise huge potential in advanced agricultural applications. However, machine vision and its precise positioning still have many technical difficulties, making it difficult for most harvesting robots to achieve true commercial applications. This article reports the application and research progress of harvesting robots and vision technology in fruit picking. The potential applications of vision and quantitative methods of localization, target recognition, 3D reconstruction, and fault tolerance of complex agricultural environment are focused, and fault-tolerant technology designed for utilization with machine vision and robotic systems are also explored. The two main methods used in fruit recognition and localization are reviewed, including digital image processing technology and deep learning-based algorithms. The future challenges brought about by recognition and localization success rates are identified: target recognition in the presence of illumination changes and occlusion environments; target tracking in dynamic interference-laden environments, 3D target reconstruction, and fault tolerance of the vision system for agricultural robots. In the end, several open research problems specific to recognition and localization applications for fruit harvesting robots are mentioned, and the latest development and future development trends of machine vision are described.

13.
J Phys Chem B ; 124(9): 1653-1664, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31955574

RESUMO

Sodium laureth sulfate (SLES) and fatty acids are common ingredients in many cosmetic products. Understanding how neutral and charged fatty acid compounds partition between micellar and water phases is crucial to achieve the optimal design of the product formulation. In this paper, we first study the formation of mixed SLES and fatty acid micelles using molecular dynamics (MD) simulations. Micelle/water partition coefficients of neutral and charged fatty acids are then calculated using COSMOmic as well as a MD approach based on the potential of mean force (PMF) calculations performed using umbrella sampling (US). The combined US/PMF approach was performed with both the additive, non-polarizable CHARMM general force field (CGenFF) and the classical Drude polarizable force field. The partition coefficients for the neutral solutes are shown to be accurately calculated with the COSMOmic and additive CGenFF US/PMF approaches, while only the US/PMF approach with the Drude polarizable force field accurately calculated the experimental partition coefficient of the charged solute. These results indicate the utility of the Drude polarizable force field as a tool for the rational development of mixed micelles.


Assuntos
Ácidos Graxos/química , Micelas , Simulação de Dinâmica Molecular , Dodecilsulfato de Sódio/análogos & derivados , Conformação Molecular , Dodecilsulfato de Sódio/química , Soluções
14.
Langmuir ; 35(33): 10855-10865, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31335154

RESUMO

Multiphase complex fluids such as micelles, microemulsions, and dispersions are ubiquitous in product formulations of foods, pharmaceuticals, cosmetics, and fine chemicals. Quantifying how active solutes partition in the microstructure of such multiphase fluids is necessary for designing formulations that can optimally deliver the benefits of functional actives. In this paper, we at first predict the structure of a heptane/butanol/sodium dodecyl sulfate droplet in water that self-assembled to form a microemulsion through the molecular dynamics (MD) simulation and subsequently investigate the thermodynamic equilibrium of solute partitioning using COSMOmic. To our knowledge, this is the first time that the MD/COSMOmic approach is used for predicting solute partitioning in a microemulsion. The predicted partition coefficients are compared to experimental values derived from retention measurements of the same microemulsion. We show that the experimental data of droplet-water partition coefficients (Kdroplet/w) can be reliably predicted by the method that combines MD simulations with COSMOmic.

15.
J Pharm Sci ; 108(9): 3003-3010, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31054887

RESUMO

Despite a number of studies showed that hair follicular pathway contributed significantly to transdermal delivery, there have been limited studies on the diffusion properties of chemicals in sebum. Here, the diffusion property of 17 chemical compounds across artificial sebum has been measured using diffusion cell. The diffusion flux showed 2 types of distinctive behaviors: that reached steady state and that did not. Mathematical models have been developed to fit the experimental data and derive the sebum diffusion and partition coefficients. The models considered the uneven thickness of the sebum film and the additional resistance of the unstirred aqueous boundary layer and the supporting filter. The derived sebum-water partition coefficients agreed well with the experimental data measured previously using equilibrium depletion method. The obtained diffusion coefficients in artificial sebum only depended on the molecular size. Change in pH for ionic chemicals did not affect the diffusion coefficients but influenced their diffusion flux because of the change of sebum-water partition coefficients. Generally, the measured diffusion coefficients of chemicals in artificial sebum are about one order of magnitude higher than those in the stratum corneum lipids, suggesting the hair follicle might have a non-negligible contribution to the overall permeation.


Assuntos
Materiais Biomiméticos/metabolismo , Sebo/metabolismo , Soluções/farmacocinética , Administração Cutânea , Materiais Biomiméticos/química , Difusão , Concentração de Íons de Hidrogênio , Permeabilidade , Sebo/química , Absorção Cutânea , Água/química
16.
Int J Pharm ; 556: 142-149, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30529662

RESUMO

The in vitro skin penetration of pharmaceutical or cosmetic ingredients is usually assessed in human or animal tissue. However, there are ethical and practical difficulties associated with sourcing these materials; variability between donors may also be problematic when interpreting experimental data. Hence, there has been much interest in identifying a robust and high throughput model to study skin permeation that would generate more reproducible results. Here we investigate the permeability of a model active, niacinamide (NIA), in (i) conventional vertical Franz diffusion cells with excised human skin or porcine skin and (ii) a recently developed Parallel Artificial Membrane Permeation Assay (PAMPA) model. Both finite and infinite dose conditions were evaluated in both models using a series of simple NIA solutions and one commercial preparation. The Franz diffusion cell studies were run over 24 h while PAMPA experiments were conducted for 2.5 h. A linear correlation between both models was observed for the cumulative amount of NIA permeated in tested models under finite dose conditions. The corresponding correlation coefficients (r2) were 0.88 for porcine skin and 0.71 for human skin. These results confirm the potential of the PAMPA model as a useful screening tool for topical formulations. Future studies will build on these findings and expand further the range of actives investigated.


Assuntos
Membranas Artificiais , Modelos Biológicos , Niacinamida/farmacocinética , Absorção Cutânea , Administração Cutânea , Animais , Ensaios de Triagem em Larga Escala/métodos , Humanos , Niacinamida/administração & dosagem , Permeabilidade , Reprodutibilidade dos Testes , Especificidade da Espécie , Suínos , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/farmacocinética
17.
Pharm Res ; 35(7): 141, 2018 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-29761237

RESUMO

PURPOSE: Sebum is an important shunt pathway for transdermal permeation and targeted delivery, but there have been limited studies on its permeation properties. Here we report a measurement and modelling study of solute partition to artificial sebum. METHODS: Equilibrium experiments were carried out for the sebum-water partition coefficients of 23 neutral, cationic and anionic compounds at different pH. RESULTS: Sebum-water partition coefficients not only depend on the hydrophobicity of the chemical but also on pH. As pH increases from 4.2 to 7.4, the partition of cationic chemicals to sebum increased rapidly. This appears to be due to increased electrostatic attraction between the cationic chemical and the fatty acids in sebum. Whereas for anionic chemicals, their sebum partition coefficients are negligibly small, which might result from their electrostatic repulsion to fatty acids. Increase in pH also resulted in a slight decrease of sebum partition of neutral chemicals. CONCLUSIONS: Based on the observed pH impact on the sebum-water partition of neutral, cationic and anionic compounds, a new quantitative structure-property relationship (QSPR) model has been proposed. This mathematical model considers the hydrophobic interaction and electrostatic interaction as the main mechanisms for the partition of neutral, cationic and anionic chemicals to sebum.


Assuntos
Fenômenos Químicos , Relação Quantitativa Estrutura-Atividade , Sebo/química , Sebo/fisiologia , Ânions , Cátions , Concentração de Íons de Hidrogênio
18.
J Agric Food Chem ; 66(12): 3137-3145, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29533635

RESUMO

Foods of high carbohydrate content such as sucrose or starch increase postprandial blood glucose concentrations. The glucose absorption system in the intestine comprises two components: sodium-dependent glucose transporter-1 (SGLT1) and glucose transporter 2 (GLUT2). Here five sappanin-type (SAP) homoisoflavonoids were identified as novel potent GLUT2 inhibitors, with three of them isolated from the fibrous roots of Polygonatum odoratum (Mill.) Druce. SAP homoisolflavonoids had a stronger inhibitory effect on 25 mM glucose transport (41.6 ± 2.5, 50.5 ± 7.6, 47.5 ± 1.9, 42.6 ± 2.4, and 45.7 ± 4.1% for EA-1, EA-2, EA-3, MOA, and MOB) than flavonoids (19.3 ± 2.2, 11.5 ± 3.7, 16.4 ± 2.4, 5.3 ± 1.0, 3.7 ± 2.2, and 18.1 ± 2.4% for apigenin, luteolin, quercetin, naringenin, hesperetin, and genistein) and phloretin (28.1 ± 1.6%) at 15 µM. SAP homoisoflavonoids and SGLT1 inhibitors were found to synergistically inhibit the uptake of glucose using an in vitro model comprising Caco-2 cells. This observed new mechanism of the glucose-lowering action of P. odoratum suggests that SAP homoisoflavonoids and their combination with flavonoid monoglucosides show promise as naturally functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels.


Assuntos
Flavonoides/farmacologia , Transportador de Glucose Tipo 2/antagonistas & inibidores , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Polygonatum/química , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Flavonoides/química , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Humanos , Hipoglicemiantes/química , Extratos Vegetais/química , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Transportador 1 de Glucose-Sódio/genética , Transportador 1 de Glucose-Sódio/metabolismo
19.
J Pharm Sci ; 107(4): 1122-1130, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29269270

RESUMO

Various neutral, cationic, and anionic chemicals contained in hair care products can be absorbed into hair fiber to modulate physicochemical properties such as color, strength, style, and volume. For environmental safety, there is also an interest in understanding hair absorption to wide chemical pollutants. There have been very limited studies on the absorption properties of chemicals into hair. Here, an experimental and modeling study has been carried out for the hair-water partition of a range of neutral, cationic, and anionic chemicals at different pH. The data showed that hair-water partition not only depends on the hydrophobicity of the chemical but also the pH. The partition of cationic chemicals to hair increased with pH, and this is due to their electrostatic interaction with hair increased from repulsion to attraction. For anionic chemicals, their hair-water partition coefficients decreased with increasing pH due to their electrostatic interaction with hair decreased from attraction to repulsion. Increase in pH did not change the partition of neutral chemicals significantly. Based on the new physicochemical insight of the pH effect on hair-water partition, a new quantitative structure property relationship model has been proposed, taking into account of both the hydrophobic interaction and electrostatic interaction of chemical with hair fiber.


Assuntos
Ânions/química , Cátions/química , Cabelo/química , Adsorção , Poluentes Ambientais/química , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Relação Quantitativa Estrutura-Atividade , Eletricidade Estática , Água/química
20.
Pharm Res ; 34(10): 2036-2048, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28660400

RESUMO

PURPOSE: The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. METHODS: The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in lipid, corneocytes, viable dermis, dermis and systemic circulation are calculated as reported previously [Pharm Res 33 (2016) 1602]. The mass transfer and partition properties in sebum are collected from existing literature. None of the model input parameters was fit to the clinical data with which the model prediction is compared. RESULTS: The integrated model has been applied to predict the published clinical data of transdermal permeation of caffeine. The relative importance of the follicular pathway is analysed. Good agreement of the model prediction with the clinical data has been obtained. The simulation confirms that for caffeine the follicular route is important; the maximum bioavailable concentration of caffeine in systemic circulation with open hair follicles is predicted to be 20% higher than that when hair follicles are blocked. CONCLUSIONS: The follicular pathway contributes to not only short time fast penetration, but also the overall systemic bioavailability. With such in silico model, useful information can be obtained for caffeine disposition and localised delivery in lipid, corneocytes, viable dermis, dermis and the hair follicle. Such detailed information is difficult to obtain experimentally.


Assuntos
Cafeína/química , Cabelo/química , Sebo/química , Administração Cutânea , Disponibilidade Biológica , Cafeína/administração & dosagem , Cafeína/farmacologia , Cafeína/toxicidade , Simulação por Computador , Derme/química , Difusão , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Epiderme/química , Cabelo/metabolismo , Folículo Piloso/química , Humanos , Lipídeos/química , Permeabilidade , Sebo/metabolismo , Absorção Cutânea , Soluções
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