The Addition of Resveratrol-Loaded Emulsions to Yogurts: Physicochemical Characterization, In Vitro Bioaccessibility and NMR-Based Nutritional Profiles.

In this study, resveratrol-loaded nano-emulsions were added to yogurts, improving the physicochemical properties and functional factors and realizing the development of nutrient-fortified yogurt. Yogurts added with free resveratrol (Y-R), resveratrol-loaded emulsions stabilized by sodium caseinate (Y-NN), decaglycerol monooleate (Y-DN), and sodium caseinate-decaglycerol monooleate (Y-DND) were evaluated for their physicochemical properties, including pH, titratable acidity, syneresis, and textural parameters, with 5-day intervals for 15-day storage. The resveratrol retention rate was analyzed in the Y-R, Y-NN, Y-DN, and Y-NDN groups during 15 days of storage. The dynamic bioaccessibility of resveratrol and the NMR-based nutritional profile of yogurt in the Y-R, Y-NN, Y-DN, and the Y-NDN group were investigated after in vitro digestion. The results demonstrated that the addition of resveratrol emulsion decreased the hardness of yogurt while evaluating its titratable acidity and water-holding capacity, which were characterized by high stability. The stability of resveratrol added in the form of an emulsion was significantly higher than that of the free form. Compared with the other groups, the yogurt formulated with sodium caseinate/decaglycerol monooleate (NaCas/DGMO) emulsion showed the highest resveratrol retention rate, about 70%. In vitro digestion showed that encapsulation effectively and persistently improved the dynamic bioaccessibility of resveratrol. Additionally, NMR-based nutritional profile analysis before and after in vitro digestion demonstrated that resveratrol emulsion nutritional fortification promoted the release of nutrients, improving the nutritional value of yogurt. These findings offered theoretical guidance and technical support for the use of resveratrol nano-emulsions in yogurt.

Characterization, interfacial rheology, and storage stability of Pickering emulsions stabilized by complex of whey protein isolate fiber and zein derived from micro-endosperm maize.

In present study, we characterized the formation, interfacial rheology, and storage stability of emulsions stabilized by microendosperm maize-derived zein (M-Zein)/whey protein isolate fiber (WPIF) nanoparticles. Microendosperm maize is a newly developed, oleic acid-rich oilseed resource. Recent research has shown that M-Zein possesses unique hydrophobic properties. Combining it with WPIF may enhance its performance as a stabilizer. Optimization of weight ratios for M-Zein/WPIF composites, guided by particle size analysis, fluorescence spectroscopy, three-phase contact angle (θ), and interfacial rheological analysis, revealed that a 4: 6 mass ratio at pH 7 yielded favorable wettability (θ = 91.2°). Interfacial rheology analysis showed that the combination of WPIF reduced M-Zein's interfacial tension to 7.2 mN/m and 36.7 mN/m at oil-water and air-water interfaces, respectively. The M-Zein/WPIF complex exhibited an elastic protein layer at the oil-water interface. Further investigations into nanoparticle concentration, oil phase volume, and pH revealed that emulsions containing 3 % nanoparticles (w/w), 50 % oil phase volume, and pH 7 showed the best storage stability. This research highlights the development of M-Zein/WPIF composited nanoparticles with superior storage stability and interfacial rheology. Additionally, it introduces a novel application for M-Zein, which elevates the value proposition of microendosperm maize.

Study on the Frying Performance Evaluation of Refined Soybean Oil after PLC Enzymatic Degumming.

It is known that phospholipase C (PLC) enzymatic degumming can hydrolyze phospholipids into diacylglycerol (DAG), which improves the efficiency of oil processing. However, it is unclear whether the presence of DAG and the use of enzymes affect the performance of the oil. This paper evaluated the frying performance of PLC-degummed refined soybean oil. Following the chicken wings and potato chips frying trials, results revealed that after 30 cycles of frying, free fatty acid (FFA) levels were 0.22% and 0.21%, with total polar compounds (TPC) at 23.75% and 24.00%, and peroxide value (PV) levels were 5.90 meq/kg and 6.45 meq/kg, respectively. Overall, PLC-degummed refined soybean oil showed almost the same frying properties as traditional water-degummed refined oil in terms of FFA, PV, TPC, polymer content, viscosity, color, foaming of frying oils, and appearance of foods. Moreover, FFA, TPC, polymer content, foaming, and color showed significant positive correlations with each other (p < 0.05) in soybean oil intermittent frying processing.

Lipid concomitant γ-oryzanol decreased oil absorbency of French fries by changing the microstructure of French fries and physical properties of frying oil.

BACKGROUND: The aim of this research was to evaluate the possibility of lipid concomitant γ-oryzanol reducing oil absorbency of fried foods and the underlying mechanism. Therefore, the influence of γ-oryzanol on moisture and oil content, and distribution and micromorphology of French fries and the viscosity, fatty acid composition and total polar compounds content of rice bran oil (RBO) after frying were studied. RESULTS: Our results showed that the incorporation of low concentration of γ-oryzanol [low addition group (LAG)] (5.754 g/kg) decreased the oil absorbency and porous structure of French fries during frying. Additionally, LAG incorporation inhibited the degradation of linoleic acid, decreased the growth rate of saturated fatty acids, total polar compounds and viscosity of frying oil. CONCLUSIONS: Consequently, it was recommended to incorporate a small amount of γ-oryzanol in frying oil because it could inhibit oil absorption behavior of French fries. © 2023 Society of Chemical Industry.

Synthesis, characterization, antibacterial and antifungal activities of 1-O-alkylglycerols.

1-O-alkylglycerols are a class of natural existing lipids with broad biological activities. However, their use in food or agricultural fields remains to be investigated, especially for their antimicrobial activity. In this work, three 1-O-alkylglycerols, 1-O-octanylglycerol (C8Gly1), 1-O-dodecylglycerol (C12Gly1), and 1-O-hexadecylglycerol (C16Gly1), were synthesized in the isolated yields of 71.3-89.8 % and characterized by 1H NMR, 13C NMR, FITR, mass spectra, and HPLC-ESLD. The critical micelle concentration (CMC) of 1-O-alkylglycerols was determined to be 1.65 mmol/L (C8Gly1), 0.33 mmol/L (C12Gly1), and 0.23 mmol/L (C16Gly1) using the pyrene method. C12Gly1 and C16Gly1 had similar surface tensions that are lower than C8Gly1. C8Gly1 can form micelles in aqueous solution with excellent nano-dispersed uniformity and stability. Furthermore, C8Gly1 and C12Gly1 not only displayed good antibacterial activity against Staphylococcus aureus, but they also inhibited the growth of Botryosphaeria dothidea, Monilia fructigena, and Phytophthora capsicum at 400 µg/mL. Thus, the C8Gly1 and C12Gly1 can serve as novel antimicrobial agents in food preservation.

Zein-Polyglycerol Conjugates with Enhanced Water Solubility and Stabilization of High Oil Loading Emulsion.

To increase the water solubility of zein as a stabilizing agent for oil-in-water (O/W) emulsions, three zein-polyglycerol (Zein-PG) conjugates, Zein-PG-2, Zein-PG-6, and Zein-PG-10, were prepared by dehydration between zein and polyglycerol aldehydes obtained by NaIO4 oxidation of polyglycerol-2, -6, and -10 and characterized by free amine content, grafting degree, Fourier transform infrared spectroscopy, and fluorescence spectra. All conjugates dispersed in water as nanoparticles were verified by transmission electron microscopy. Conjugation with PG changed the isoelectric point of zein from 6.2 to 6.8 and to 4.0. Zein-PG-6 and Zein-PG-10 showed strong stabilization on the O/W emulsions with 18-fold loading of soybean oil on the basis of conjugate mass, displaying high oil loading capacity. Confocal laser scanning microscopy (CLSM) confirmed the O/W structure of emulsions and that the absorption of Zein-PG-10 on the oil droplet surface offered the driving force to be stable. The present Zein-PG conjugates thus produced an enticing resource for use as nanocarriers or bioemulsifiers in food or pharmaceutical industries.

Improved Physicochemical Properties of Curcumin-Loaded Solid Lipid Nanoparticles Stabilized by Sodium Caseinate-Lactose Maillard Conjugate.

To improve the water solubility, antioxidant activity, and chemical stability of curcumin, solid lipid nanoparticles (SLNs) were fabricated using equal masses of propylene glycol monopalmitate and glyceryl monostearate as the lipid matrix and sodium caseinate-lactose (NaCas-Lac) Maillard conjugate as the emulsifier. The entrapment efficiency was more than 90% when curcumin was 2.5% and 5.0% of lipid mass, and the SLNs were stable during 30-day storage. SLNs stabilized by NaCas-Lac showed better physicochemical properties than those prepared with NaCas, including higher sphericity and homogeneity; higher entrapment efficiency; better stability against pH, ionic strength, and simulated gastrointestinal digestions; and more controlled release. SLNs also greatly enhanced the antioxidant activity of encapsulated curcumin and the retention of curcumin during storage. Therefore, the present SLNs may find applications to deliver lipophilic compounds in functional foods and beverages.

Carvacrol Loaded Solid Lipid Nanoparticles of Propylene Glycol Monopalmitate and Glyceryl Monostearate: Preparation, Characterization, and Synergistic Antimicrobial Activity.

To develop solid lipid nanoparticles (SLNs) with stable lipid matrix structures for the delivery of bioactive compounds, a new class of SLNs was studied using propylene glycol monopalmitate (PGMP) and glyceryl monostearate (GMS) mixtures and carvacrol as a model lipophilic antimicrobial. Stable SLNs were fabricated at PGMP:GMS mass ratios of 2:1 and 1:1, and the carvacrol loading was up to 30% of lipids with >98% encapsulation efficiency and absence of visual instability. Fluorescence spectra and release profiles indicated the carvacrol was successfully encapsulated and homogeneously distributed within the SLNs. SLNs fabricated with equal masses of PGMP and GMS had better stability of carvacrol during storage and higher sphericity than those with a ratio of 2:1 and were much more effective than free carvacrol against Escherichia coli O157:H7 and Staphylococcus aureus. These findings demonstrated the potential applications of the studied SLNs in delivering lipophilic bioactive compounds in food and other products.

1-Laurin-3-Palmitin as a Novel Matrix of Solid Lipid Particles: Higher Loading Capacity of Thymol and Better Stability of Dispersions Than Those of Glyceryl Monostearate and Glyceryl Tripalmitate.

To develop solid lipid nanoparticles (SLNs) with a new lipid matrix for delivery of hydrophobic bioactive molecules, high purity 1-laurin-3-palmitin (1,3-LP) was synthesized and the prepared 1,3-LP SLNs were compared with those of two common SLN matrices in glyceryl monostearate (GMS) and glyceryl tripalmitate (PPP). Conditions of preparing SLNs were first optimized by evaluating the particle size, polydispersity index (PDI), zeta-potential, and stability. Thereafter, the performance of SLN loading of a model compound in thymol was studied. The loading capacity of thymol in 1,3-LP SLNs was 16% of lipids and higher than 4% and 12% for GMS- and PPP-SLNs, respectively. The 1,3-LP SLNs also had the best efficiency to entrapment thymol during the prolonged storage. X-ray diffraction (XRD) analyses confirmed the excellent crystalline stability of 1,3-LP leading to the stable entrapment efficiency and better stability of thymol-loaded SLNs. Conversely, the polymorphic transformation of GMS and PPP resulted in the declined entrapment efficiency of thymol in the corresponding SLNs. This work indicated the 1,3-diacylglycerol (DAG) SLNs could be used as a promising delivery system for the encapsulation of hydrophobic bioactive molecules with high loading capacity and stability.

Core-Shell Nanoencapsulation of α-Tocopherol by Blending Sodium Oleate and Rebaudioside A: Preparation, Characterization, and Antioxidant Activity.

Nanoencapsulation of α-tocopherol (α-TOC) by blending sodium oleate (NaOl) and rebaudioside A (RebA) was successfully prepared by self-assembly method under mild conditions. The optimized nanoemulsion showed the loading capacity of α-TOC was 30 wt% of sodium oleate. FTIR analysis suggested that hydrogen bonds and hydrophobic interactions were the major forces in α-TOC-NaOl/RebA complexes that were spherical and possessed well-distinguishable core-shell structures. The freeze-dried α-TOC-NaOl/RebA complexes had great stability under ambient conditions. The release profile of α-TOC showed a first-order kinetics reaching around 67.9% after 90 h at 25 °C. Nanoencapsulation improved dispersibility and greatly increased the antioxidant activity of α-TOC. Therefore, the stable α-TOC-NaOl/RebA core-shell complexes prepared from "generally recognized as safe" (GRAS) ingredients have great potential to supplement α-TOC in food and cosmetic products.

Risk factors and biomarkers of non-alcoholic fatty liver disease: an observational cross-sectional population survey.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a major public health burden in China, and its prevalence is increasing. This study aimed to determine the risk factors and biomarkers of NAFLD. DESIGN: An observational cross-sectional primary survey. SETTING: Central China. PARTICIPANTS: The study included 1479 participants aged over 18 and below 80 years, not currently being treated for cancer or infectious disease or no surgery in the previous year, and no history of cancer or an infectious disease. Participants underwent clinical examination, metabolomic assay and anthropometric assessment. Univariate and logistic regression analyses were used to evaluate associations between covariates and NAFLD. MAIN OUTCOME MEASURES: Risk factors and metabolic biomarkers including sex, body mass index, hypertension, body fat ratio, blood triglycerides, blood fasting glucose, liver enzyme elevation, uric acid and oleic acid-hydroxy oleic acid (OAHOA). RESULTS: Data from the 447 participants (mean age 44.3±11.9 years) were analysed, and the prevalence of NAFLD was 24.7%. Male sex (OR 3.484, 95% CI 2.028 to 5.988), body mass index ≥24 kg/m2 (OR 8.494, 95% CI 5.581 to 12.928), body fat ratio (≥25 for women, ≥20 for men) (OR 1.833, 95% CI 1.286 to 2.756), triglycerides ≥1.7 mmol/L (OR 1.340, 95% CI 1.006 to 1.785), fasting glucose ≥6.1 mmol/L (OR 3.324, 95% CI 1.888 to 5.850), blood pressure ≥140/90 mm Hg or antihypertensive drug treatment (OR 1.451, 95% CI 1.069 to 1.970), uric acid (≥357 µmol/L for women, ≥416 µmol/L for men) (OR 2.755, 95% CI 2.009 to 3.778) and OAHOA (<5 nmol/L) (OR 1.340, 95% CI 1.006 to 1.785) were independent predictors of NAFLD (all P<0.05). These results were verified by all 1479 participants. CONCLUSIONS: NAFLD was common among the study participants. In particular, NAFLD was correlated with uric acid. We identified OAHOA as a novel marker of NAFLD prevalence. It provides a reference on the prevention of NAFLD and related metabolic diseases with the rapid urbanisation, technological advancement and population ageing in China over the recent decades.

Dynamic lipid profile of hyperlipidemia mice.

Biomarkers of serum fatty acids in hyperlipidemia need to be elucidated. 90 SPF KM male mice were randomly divided into 18 groups (n=5/group), control groups, and high fat diet (HFD) groups at 9 time points. On day 7, 10, 15, 18, 21, 24, 28, 31, and 35, the mice were sacrificed; blood was collected into tubes from the eyes, serum samples for clinical biochemistry assays and gas chromatography-mass spectroscopy were attained after centrifugation, and the contents of serum fatty acids were detected with GC-MS. Sections of livers were taken and stored in formalin solution for histological assessments. No species differences existed in all these groups. The contents of C16:1, C18:1, C22:6 were significantly different between HFD groups and the corresponding controls; meanwhile, the proportion of fatty acids, especially the monounsaturated degree, the polyunsaturated degree, changed significantly and regularly (P<0.05). Thus the three unsaturated fatty acids C16:1, C18:1, C22:6 and the monounsaturated/polyunsaturated unsaturated degrees may be as potential biomarkers of hyperlipidemia.

Structural characterization and physicochemical properties of protein extracted from soybean meal assisted by steam flash-explosion with dilute acid soaking.

The aim of this work was to analyze the influence of steam flash-explosion (SFE) with dilute acid soaking pretreatment on the structural characteristics and physiochemical properties of protein from soybean meal (SBM). The pretreatment led to depolymerisation of soy protein isolate (SPI) and formation of new protein aggregation through non-disulfide covalent bonds, which resulted in broader MW distribution of SPI. The analysis of CD spectroscopy showed that the SFE treatment induced minor changes in secondary structure, however, the intrinsic tryptophan fluorescence revealed that acid soaking and SFE treatment pronouncedly altered the tertiary structure of SPI. The protein zeta potential was shown to be increased after SFE treatment attributed to the changes in protein structure and the covalent coupling between carbohydrate and protein. These results contribute to clarifying the mechanisms of the effect of pretreatment on SPI structure, thus moving further toward implementing SFE in the processing chain of SPI.

A novel approach of periodate oxidation coupled with HPLC-FLD for the quantitative determination of 3-chloro-1,2-propanediol in water and vegetable oil.

A novel approach of periodate oxidation coupled with high-performance liquid chromatography (HPLC)-fluorescence detection (FLD) for the quantitative determination of 3-chloro-1,2-propanediol (3-MCPD) has been established. The essence of this approach lies in the production of chloroacetaldehyde by the oxidization cleavage of 3-MCPD with sodium periodate and the HPLC analysis of chloroacetaldehyde monitored by an FLD detector after fluorescence derivatization with adenine. The experimental parameters relating to the efficiency of the derivative reaction such as concentration of adenine, chloroacetaldehyde reaction temperature, and time were studied. Under the optimized conditions, the proposed method can provide high sensitivity, good linearity (r(2) = 0.999), and repeatability (percent relative standard deviations between 2.57% and 3.44%), the limits of detection and quantification were 0.36 and 1.20 ng/mL, respectively, and the recoveries obtained for water samples were in the range 93.39-97.39%. This method has been successfully applied to the analysis of real water samples. Also this method has been successfully used for the analysis of vegetable oil samples after pretreatment with liquid-liquid extraction; the recoveries obtained by a spiking experiment with soybean oil ranged from 96.27% to 102.42%. In comparison with gas chromatography or gas chromatography-mass spectrometry, the proposed method can provide the advantages of simple instrumental requirement, easy operation, low cost, and high efficiency, thus making this approach another good choice for the sensitive determination of 3-MCPD.

Preparation and characterization of phosphatidylcholine-coated zirconia-magnesia stationary phase for artificial membrane chromatography.

Immobilized artificial membrane chromatography stationary phase was prepared by coating soybean phosphatidylcholine (PC) on zirconia-magnesia micro-particles. The stability and chromatographic properties were investigated and compared with the PC-coated silica chromatography stationary phase prepared by the same method. PC-coated zirconia-magnesia chromatography stationary phase was more stable than the silica especially on resisting organic solvents. Hydrophobic action was the main factor for the retention of analyte on the new artificial membrane chromatography stationary phase, and electrostatic interaction had some contribution to retention. In addition, the special interaction between analyte and matrix affected retention greatly. Basic solutes were appropriate to be analyzed on PC-coated zirconia-magnesia stationary phase and acidic solutes were appropriate to be done on the silica one. Hence, the two different matrices artificial membrane stationary phases were perfectly complementary.

Microemulsions as nanoreactors to produce whey protein nanoparticles with enhanced heat stability by sequential enzymatic cross-linking and thermal pretreatments.

Sequential enzymatic cross-linking and heat pretreatments were used in this work to enhance the heat stability of whey protein isolate (WPI). In the first route, WPI was cross-linked by transglutaminase before incorporation in microemulsions for heat pretreatment at 90 degrees C for 20 min. In the second route, WPI was cross-linked by transglutaminase within microemulsions before thermal pretreatment. Particles produced from the two routes were different in dimension and heat stability and were also affected by the ratio of WPI and enzyme and cross-linking duration. At appropriate conditions, for example, 10 h of cross-linking by transglutaminase equivalent to 5% mass of WPI using the first route, a 5% dispersion (pH 6.8 and 100 mM NaCl) of the produced nanoparticles remained clear after heating at 90 degrees C for 20 min. In comparison, nanoparticles produced by thermal pretreatment only in a microemulsion corresponded to a translucent, flowable dispersion, whereas native WPI formed a gel. This novel approach can be used to manufacture heat-stable whey protein ingredients for clear beverage applications.

[Preparation of magnesia-zirconia based mimetic biomembrane stationary phase and its applications in evaluating drug-membrane interactions].

A novel mimetic biomembrane chromatographic stationary phase of magnesia-zirconia composite matrix was prepared based on the Lewis acid-base interaction between the phosphonate group of phosphatidylcholine residue and the Lewis acid sites of magnesia-zirconia composite. The infrared absorption spectrum and X-ray photoelectron spectrum of the stationary phase illustrated that the magnesia-zirconia composite was successfully modified with phosphatidylcholine. The interactions between the membrane and the drugs were evaluated. It is observed that the log Kmbm values have good relationships with the log Papp, and the linear slope is 1.049, which is near unity. Moreover, on the basis of the thermodynamics derivation, the difference in standard free energies (delta (delta G0)) is introduced to describe the drug-membrane interaction. The results show that the log Kmbm, and delta (delta G0) value provide key information on the transport properties of the drugs. The establishment of this chromatographic model may be a new way for the evaluation of the drug-membrane interactions.

Dynamic NMR study and theoretical calculations on the conformational exchange of valsartan and related compounds.

Valsartan (1), an antihypertensive drug of the sartan family, and three related compounds, 3-methyl-2-((2'-(1-methyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl) pentanoylamino)butyric acid (2), 3-isopropyl-6-propyl-4-(2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl) morpholine-2,5-dione (3), and 3-isopropyl-6-propyl-4-(4'-(1H-tetrazol-5-yl)biphenyl4-ylmethyl) morpholine-2,5-dione (4), were studied by nuclear magnetic resonance (NMR) spectroscopy. Assignment of (1)H and (13)C NMR resonances for the compounds were completed using COSY, HSQC and HMBC techniques. It was found that each of the compounds 1, 2, and 4 had two sets of (1)H and (13)C resonances, suggesting the presence of two conformers in solution. Based on NOESY experiments at different temperatures, thermodynamic parameters of the conformational exchange process were deduced for these compounds. The exchange barrier was found to be 17.9 +/- 0.7, 18.5 +/- 0.8, and 17.7 +/- 0.6 kcal mol(-1) with the corresponding free energy difference (DeltaG) of 0.32 +/- 0.04, 0.23 +/- 0.01, and 0.13 +/- 0.04 kcal mol(-1) for 1, 2, and 4, respectively, at 298 K. Two conformations of valsartan were elucidated by NMR spectroscopy and quantum chemistry calculation. The results showed that two conformers of valsartan interchange via rotation about the C(O)--N bond.

Implementation of real-time two-dimensional nuclear magnetic resonance spectroscopy for on-flow high-performance liquid chromatography.

Directly coupled HPLC-NMR has become a powerful tool for separation and structural elucidation of unknown compounds. However, there are only a few reports on application of on-flow two-dimensional (2D) NMR in HPLC-NMR. Here we present an alternative method for recording real-time 2D-NMR spectrum (total correlation spectroscopy, TOCSY) on a commercial HPLC-NMR system. The method is based on well-established Hadamard matrix for 2D-NMR frequency encoding. In addition, a modified/improved solvent suppression approach is incorporated. This makes it possible to carry out the experiment with both polar and gradient eluents, the widely used chromatographic conditions. The method is example using a synthesized mixture of three amino acids (His, Phe and Try) and a human urine sample. The method demonstrated here may be utilized for high-throughput structural or unknown component identification and fast dynamic study in a variety of applications.

Magnesia-zirconia based mimetic biomembrane chromatography for predicting human drug absorption.

In this paper, a novel mimetic biomembrane chromatography stationary phase of magnesia-zirconia composite matrix were prepared with the Lewis acid-base interaction between phosphatidylcholine's residue phosphonate group and Lewis acid sites of magnesia-zirconia composite; the retention factors of a chemically diverse set of drugs on the new stationary phase were determined; the drugs logK(mbm) values were correlationed with the absorbed fraction of drugs orally administered in humans (%F(a)) and a hyperbolic relationship was obtained. Meanwhile, the relationship between the logK(mbm) values and hydrophobic parameters (logP(oct) and logD(oct)) were discussed. The usefulness of the new column for predicting oral drug absorption in humans is demonstrated by comparing this model with IAM, ILC and BMC models. Results show that the logK(mbm) values have good relationship with logK(W)(IAM), logK(BMC) and have moderate to fair relationship with logK(s) determined on four different ILC column (EPL, PC, PC-PE, PC-PS). Therefore, the logK(mbm) values can provide key information about the transport properties of drugs and this chromatographic model may be applicable for prediction of drug uptake through epithelial cell membranes during the drug discovery process.