Objective:To correlate the chromatographic and computational method to calculate lipophilicity of selected ginger compounds and to observe the effects of log P on wound healing.Methods:Mixtures of acetonitrile and wat...Objective:To correlate the chromatographic and computational method to calculate lipophilicity of selected ginger compounds and to observe the effects of log P on wound healing.Methods:Mixtures of acetonitrile and water with acetonitrile content between 95%and 50%v/v in 5%increments were kept separately in 10 different chromatographic chambers,saturated with solvent for 2 h.Spots were observed under UV light atλ=254 nm p-anisaldehyde used as a spraying reagent Theoretical calculation was done using the Alogps 2.1 online program at www.vcclab.org/lab/alogps.For percentage wound contraction,five groups of animal(mice)(25-30 g)of either sex were selected.Wound were created on dorsal surface of animals using toothed forceps,scalpel and pointed scissors.The wound areas were calculated using vernier caliper.After making wound mice were orally administered 35 mg/kg 6-shogoal,6-gingerol,8-gingerol and 10-gingerol respectively.Croup E as the control group received tap water.Results:The Iipophilicity values determined in thin layer chromatography were correlated with the theoretically calculated various log P by linear regression analysis.Significant correlations were found between log P values calculated by software program and the experimental reversedphase thin-layer chromatography data.Order of wound healing property of ginger compounds is directly dependent on lipophilieity i.e.more lipophilic compound has highest activity.Conclusions:Experimentally determined lipophilieity(R_(MO))values were correlated with log P determined by software's and found satisfactory.Lipophilieity(R_(MO)is a useful parameter for the determination and prediction of biological activity of ginger compounds.展开更多
Objectives: To evaluate the barrier function of different skin layers in the process of percutaneous drug absorption. Methods: In vitro permeability via intact or stripped skin of 6 drugs (5-fluorouracil, theo-phyllin...Objectives: To evaluate the barrier function of different skin layers in the process of percutaneous drug absorption. Methods: In vitro permeability via intact or stripped skin of 6 drugs (5-fluorouracil, theo-phylline, hydroquinone, barbital, isosorbide dinitrate and ketoprofen) with a wide span of lipophilicity were investigated in the patch dosage forms. Results: Characteristic parabolic relations was observed between the permeability (Kp, cm/h) of the drugs with different lipophilicity and their LogPc via either intact or stripped skin. However, due to the absence of the stratum corneum, increased Kp ratio for the tested drugs was proportional to their solubility in water other than their LogKp. When isopropyl myristate was used as absorption promoter of the drugs, the parabolic relationship no longer existed. For the intact skin, increase of Kp ratio of the drugs was enhanced resulting from IPM as drug's LogPc decreased. On the other hand, in the case of stripped skin, this enhancement was positively related to the solubility of the drugs in IPM. Conclusion : These data and methods present a novel approach to describe percutaneous drug absorption via damaged or diseased skin.展开更多
Reliable prediction of lipophilicity in organic compounds involves molecular descriptors determination. In this work, the lipophilicity of a set of twenty-three molecules has been determined using up to eleven quantum...Reliable prediction of lipophilicity in organic compounds involves molecular descriptors determination. In this work, the lipophilicity of a set of twenty-three molecules has been determined using up to eleven quantum various descriptors calculated by means of quantum chemistry methods. According to Quantitative Structure Property Relationship (QSPR) methods, a first set of fourteen molecules was used as training set whereas a second set of nine molecules was used as test set. Calculations made at AM1 and HF/6-311++G theories levels have led to establish a QSPR relation able to predict molecular lipophilicity with over 95% confidence.展开更多
QSAR methodology was used to assess the effects of lipophilicity (logP), molar volume (MV) and polarizability (pl) of the side chains at N2 and C5 of 20 known desoxy anthrapyrazoles on their in vitro anticancer activi...QSAR methodology was used to assess the effects of lipophilicity (logP), molar volume (MV) and polarizability (pl) of the side chains at N2 and C5 of 20 known desoxy anthrapyrazoles on their in vitro anticancer activity expressed as the negative logarithm of the inhibitory concentration of 50% of L1210 murine leukemia cell line (1/logIC50). The main data set shows poor correlations between biological response and the descriptors with exception of MV of the C5 side chain, where a moderate correlation was discerned ( =0.60, n = 18, two outliers). To extract more information regarding mechanism, the main data set was visually classified to three clusters depending on N2 side chain. Cluster 1 containing six 5-substituted 2-[(2-hydroxyethyl) amino] ethyl anthrapyrazoles;cluster 2 contains ten 5-subsitutes 2-(diethyl amino) ethyl anthrapyrazoles and cluster 3 contains four anthrapyrazoles with miscellaneous substituents at both N2 and C5. For cluster 1, MV and pl of C5 show high correlation with biological response (R2’s = 0.75 and 0.72 respectively) while logP gives a weak correlation (R2 = 0.44). For cluster 2, the correlations of logP and pl of C2side chain are higher (=0.66 and 0.62 respectively) compared with MV (=0.16). Cluster 3 shows very poor correlation with all descriptors (~0.3). This indicates mechanistic distinction between the three clusters. Derived descriptors which represent the difference between the descriptors of N2 and C5 side chains where used to explore the presence of interplay between these descriptors in affecting variability of the biological response.展开更多
Melamine sponge is a major concern for oil-water separation due to its lightweight,high porosity(>99%),cost-effectiveness,impressive mechanical properties,and chemical/thermal stability.However,its amphiphilic natu...Melamine sponge is a major concern for oil-water separation due to its lightweight,high porosity(>99%),cost-effectiveness,impressive mechanical properties,and chemical/thermal stability.However,its amphiphilic nature hinders selective oil absorption in water.Recent strategies to enhance hydrophobicity are reviewed,including synthetic methods and materials,with comprehensive explanations of the mechanisms driven by surface energy and roughness.Key performance indicators for MS in oil-water separation,including adsorption capacity,wettability,stability,emulsion separation,reversible wettability switching,flame retardancy,mechanical properties,and recyclability,are thoroughly discussed.In conclusion,this review provides insights into the future potential and direction of functional melamine sponges in oil-water separation.展开更多
Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obes...Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.展开更多
Using methanol-water mixtures as the mobile phase, the chromatographic retention parameters k' and Rf were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and reversed-phase high-perf...Using methanol-water mixtures as the mobile phase, the chromatographic retention parameters k' and Rf were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and reversed-phase high-performance thin-layer chromatography (RP-HPTLC) for N-(benzothiazol-2-yl)-α-amino alkyl phosphoric diesters and the correlation with lipophilicity parameter (Clog P) was established. Log Kw values obtained from RP-HPLC and Rm values obtained from RP-HPTLC can be used to evaluate the lipophilicity of this kind of compounds. Chromatographic method is a good alternative for lipophilicity measurement.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indica...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics.However,it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD.AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD.METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD.The difference in HCC risk between statin users and non-users was calculated among MASLD patients.We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction.RESULTS A total of four studies consisting of 291684 patients were included.MASLD patients on statin therapy had a 60%lower pooled risk of developing HCC compared to the non-statin group[relative risk(RR)=0.40,95%CI:0.31-0.53,I2=16.5%].Patients taking lipophilic statins had a reduced risk of HCC(RR=0.42,95%CI:0.28-0.64),whereas those on hydrophilic statins had not shown the risk reduction(RR=0.57,95%CI:0.27-1.20).The higher(>600)cumulative defined daily doses(cDDD)had a 70%reduced risk of HCC(RR=0.30,95%CI:0.21-0.43).There was a 29%(RR=0.71,95%CI:0.55-0.91)and 43%(RR=0.57,95%CI:0.40-0.82)decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD,respectively.CONCLUSION Statin use lowers the risk of HCC in patients with MASLD.The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.展开更多
Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we...Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.展开更多
Objective The entorhino-hippocampal pathway is the major excitatory input from neurons of the entorhinal cortex on both ipsilateral and contralateral hippocampus/dentate gyrus. This fiber tract consists of the alvear ...Objective The entorhino-hippocampal pathway is the major excitatory input from neurons of the entorhinal cortex on both ipsilateral and contralateral hippocampus/dentate gyrus. This fiber tract consists of the alvear path, the perforant path and a crossed commissural projection. In this study, the histogenesis and development of the various subsets of the entorhino-hippocampal projection have been investigated. Methods Dil, DiO and fast blue tracing as well as anti-calretinin immunocytochemistry were carried out with prenatal and postnatal rats at different ages. Results The alvear path and the commissural pathway started to develop as early as embryonic day （E） 16, while the first perforant afferents reached the stratum lacunosum-moleculare of the hippocampus at E 17 and the outer molecular layer of dentate gyrus at postnatal day （P） 2, respectively. Retrograde tracing with DiI identified entorhinal neurons in layer II to IV as the origin of entorhino-hippocampal pathway. Furthermore, anti-calretinin immunocytochemistry revealed transitory Cajal- Retzius （CR） cells in the stratum lacunosum-moleculare of the hippocampus from as early as E 16. DiI labeling of entorhinal cortex fibers and combined calretinin-immunocytochemistry showed a close association between CR cells and entorhinal afferents. Conclusion The subsets of entorhino-hippocampal pathway appear in the developmental hippocampus during El6 - P2. The temporal and spatial relationship between CR cell and perforant afferent suggests the role of this cell type as a guiding cue for entorhinal afferents at early cortical development.展开更多
Aim To investigate the relationship between pH environment of meptazinolhydrochloride (MEP) and its nasal absorption. Methods In situ nasal peifusion was performed to studythe effect of pH environment on the nasal abs...Aim To investigate the relationship between pH environment of meptazinolhydrochloride (MEP) and its nasal absorption. Methods In situ nasal peifusion was performed to studythe effect of pH environment on the nasal absorption. Its effect on the transport from nose tobrain was further researched by in vivo experiment. Results In in situ perfusion experiment, thenasal absorption of MEP in basic environment was significantly higher than that in acid condition,but the difference was not observed in in vivo experiment. Conclusion The pH environment ofmeptazinol hydrocloride in formulation cannot be regarded as an important factor influencing nasalabsorption and transport from nose to brain.展开更多
Ocular drug delivery is one of the most attention-grabbing and challenging endeavors among the numerous existing drug delivery systems.From a drug delivery point of view,eye is an intricate organ to investigate and ex...Ocular drug delivery is one of the most attention-grabbing and challenging endeavors among the numerous existing drug delivery systems.From a drug delivery point of view,eye is an intricate organ to investigate and explore.In spite of many limitations,advancements have been made with the intention of improving the residence time or permeation of the drug in the ocular region.Poor bioavailability of topically administered drugs is the major issue pertaining to ocular drug delivery.Several efforts have been made towards improving precorneal residence time and corneal penetration,e.g.iontophoresis,prodrugs and ionpairing,etc.Prodrug approach(chemical approach)has been explored by the formulation scientists to optimize the physicochemical and biochemical properties of drug molecules for improving ocular bioavailability.Formulation of ocular prodrugs is a challenging task as they should exhibit optimum chemical stability as well as enzymatic liability so that they are converted into parent drug after administration at the desired pace.This review will encompass the concept of derivatization and recent academic and industrial advancements in the field of ocular prodrugs.The progression in prodrug designing holds a potential future for ophthalmic drug delivery.展开更多
Corn cob is a naturally renewable material with developed micropore and hydrophobic characteristics, which enables it to show good oil adsorption capacity. In order to improve oil adsorption capacity, corn cob was mod...Corn cob is a naturally renewable material with developed micropore and hydrophobic characteristics, which enables it to show good oil adsorption capacity. In order to improve oil adsorption capacity, corn cob was modified with lauric acid and ethanediol. The structure of raw and modified corn cob was investigated using Fourier transform infrared(FTIR) spectroscopy, scanning electron microscopy(SEM), Brunauer-Emmett-Teller(BET) method, thermogravimetric analysis(TGA) and Ze Ta potential analyzer. The effects of p H level, adsorption time, adsorbent dosage, and initial oil concentration on oil absorbency of corn cob were studied. The results indicate that the modification significantly improved the lipophilicity of corn cob, making the modified corn cob with much better adsorption capacity on oil absorbency. Compared with raw corn cob, the maximum saturated adsorption capacity of modified corn cob is 16.52 mg/g at p H 5, and the increasing percentage is found to be 141%, which indicates that the modification causes a better adsorption capacity for oil removal. In addition, due to high oil adsorption capacity, affordable price and low secondary pollution, the modified corn cob could be considered promising alternative for the traditional oil adsorbent to clean up the emulsified oily water.展开更多
The first combined experimental and theoretical study on the ionization and lipophilic properties of peptide nucleic acid(PNA)derivatives,including eleven PNA monomers and two PNA decamers,is described.The acidity con...The first combined experimental and theoretical study on the ionization and lipophilic properties of peptide nucleic acid(PNA)derivatives,including eleven PNA monomers and two PNA decamers,is described.The acidity constants(pKa)of individual acidic and basic centers of PNA monomers were measured by automated potentiometric pH titrations in water/methanol solution,and these values were found to be in agreement with those obtained by MoKa software.These results indicate that single nucleobases do not change their pKa values when included in PNA monomers and oligomers.In addition,immobilized artificial membrane chromatography was employed to evaluate the lipophilic properties of PNA monomers and oligomers,which showed the PNA derivatives had poor affinity towards membrane phospholipids,and confirmed their scarce cell penetrating ability.Overall,our study not only is of potential relevance to evaluate the pharmacokinetic properties of PNA,but also constitutes a reliable basis to properly modify PNA to obtain mimics with enhanced cell penetration properties.展开更多
Two acidic carbon materials （H-PRC and HS-C） were used as catalysts for the condensation reaction of methanol with formaldehyde to produce dimethoxymethane （DMM） in aqueous solution （hydrophilic system） and for ...Two acidic carbon materials （H-PRC and HS-C） were used as catalysts for the condensation reaction of methanol with formaldehyde to produce dimethoxymethane （DMM） in aqueous solution （hydrophilic system） and for the etherification of isopentene with methanol to produce tert amyl methyl ether （TAME） in toluene solution （lipophilic system）. Microcalorimetric adsorptions of water and benzene showed that the HS-C was highly hydrophilic without the lipophilicity, while the H-PRC exhibited both the hydrophilicity and lipophilicity. Thus, the HS-C was well dispersed in aqueous solution and difficult to separate from it. On the other hand, the H-PRC was highly active, more active than the acidic resin （D008） and sulfuric acid, for the synthesis of DMM in aqueous solution. The H-PRC was also highly active, more active than the HS-C, for the etherification of isopentene with methanol to produce TAME in toluene solution, probably owing to its amphiphilic surface property as well as its strong surface acidity as measured by the microcalorirnetric adsorption of NH3.展开更多
The kinetics of ecotoxicant transport through the membrane was studied. The ecotoxicants studied were pecticides widely used in agriculture: lontrel (clopyralid), sencor (metribuzin), basagran (bentazon), roundup (gly...The kinetics of ecotoxicant transport through the membrane was studied. The ecotoxicants studied were pecticides widely used in agriculture: lontrel (clopyralid), sencor (metribuzin), basagran (bentazon), roundup (glyphosate), kusagard (alloxydim sodium), and sethoxydim, as well as lontrel complexes with cobalt and copper. All compounds considered penetrate through the model phosphatidylcholine liposomal membranes. The transfer rate was monitored by fluorescence quenching of ?-ATP inside the liposomes. The mathematical model for the process was proposed, and the mass transfer rates were calculated. The octanol/water partition constants were determined. All the compounds con- sidered were shown to accumulate in the fatty layer. The kinetics of their accumulation was studied, and the rates of accumulation in the nonpolar phase were calculated, which correlate with the complexation constants of the same compounds. Bioaccumulation of the toxicants is caused by the formation of complexes with the fatty phase (lipid part) of the cellular membranes. The toxicants under study transferred into the nonpolar phase with a considerable rate dur- ing the whole observation time, namely, 18 months.展开更多
The retention behavior and lipophilicity parameters of some antiphychotics were determined using reversed-phase thin layer chromatography. Quantitative structure-activity relationships studies have been performed to c...The retention behavior and lipophilicity parameters of some antiphychotics were determined using reversed-phase thin layer chromatography. Quantitative structure-activity relationships studies have been performed to correlate the molecular characteristics of observed compounds with their retention as well as with their chromatographically determinated lipophilicity parameters. The effect of different organic modifiers (acetone, tetrahydrofuran, and methanol) has been studied. The retention of investigated compounds decreases linearly with increasing concentration of organic modifier. The chemical structures of the antipsychotics have been characterized by molecular descriptors which are calculated from the structure and related to chromatographically determinated lipophilicity parameters by multiple linear regression analysis. This approach gives us the possibility to gain insight into factors responsible for the retention as well as lipophilicity of the investigated set of the compounds. The most prominent factors affecting lipophilicity of the investigated substances are Solubility, Energy of the highest occupied molecular orbital, and Energy of the lowest unoccupied molecular orbital. The obtained models were used for interpretation of the lipophilicity of the investigated compounds. The prediction results are in good agreement with the experimental value. This study provides good information about pharmacologically important physico-chemical parameters of observed antipsychotics relevant to variations in molecular lipophilicity and chromatographic behavior. Established QSAR models could be helpful in design of novel multitarget antipsychotic compounds.展开更多
A 12-month program of monitoring potentially toxic microalgae(that produce lipophilic shellfi sh toxins; LSTs) and their toxins in bivalves was conducted from April 2006 to March 2007 in the Nanji Islands, East China ...A 12-month program of monitoring potentially toxic microalgae(that produce lipophilic shellfi sh toxins; LSTs) and their toxins in bivalves was conducted from April 2006 to March 2007 in the Nanji Islands, East China Sea. Two Dinophysis species, D. caudata and D. acuminata, were identifi ed, and D. caudat a was found to be the dominant species. D. caudata was detected in water samples between April and June 2006, and between February and March 2007. It reached its highest abundances in May, with a mean abundance of 1.38×10 2 cells/L in surface water and 1.25×10 2 cells/L in bottom water(<10 m deep). The temporal distribution of D. caudata was associated with the occurrence of LSTs in bivalve samples, which mostly occurred at the same time as D. caudata blooms, between April and July 2006. All of the cultured bivalves sampled between April and June were contaminated with LSTs, with an average toxicity of 85 μg okadaic acid(OA) eq./100 g meat, which was four times higher than the Chinese regulatory limit(20 μg OA eq./100 g meat). Ten out of fi fteen wild samples(66.7%) collected during the same period were positive for LSTs, and contained an average LST toxicity of 45 μg OA eq./100 g meat(more than twice the regulatory value). Cultured Patinopecten yessoensis collected on 15 May 2006 had the highest toxicity, 320 μg OA eq./100 g meat, and relatively high toxicities(80 to 160 μg OA eq./100 g meat) were found in bivalves until the end of July.展开更多
The chemical compositions of the dichloromethane extracts of inner and outer barks from six Pinus species（P.elliotii,P.oocarpa,P.caribeae,P.merkusii,P.montezumae,and P.insularis） grown in Indonesia were investigated...The chemical compositions of the dichloromethane extracts of inner and outer barks from six Pinus species（P.elliotii,P.oocarpa,P.caribeae,P.merkusii,P.montezumae,and P.insularis） grown in Indonesia were investigated by GC and GC–MS.Generally,the amounts of extractive contents were higher in the inner bark than in the outer bark except for P.merksuii.Fatty acids,monoterpenes,sesquiterpenes,resin acids,triterpenoids,and steroids were detected and quantified.Inner and outer barks differed not only in content of these compounds but also in their composition.Fatty acids and alcohols were the major classes of lipophilic compounds in the outer bark of P.caribeae, P.insularis,and P.montezumae.Steroids and triterpenoids were the dominant compounds identified in the inner bark of P.elliotii,P.insularis,and P.merkusii.Resin acids were the most abundant group in the inner bark of P.oocarpa whereas monoterpenes and sesquiterpenes were recorded in minor quantities in both bark layers of all species.展开更多
基金Supported by the deanship at King Saud University with Grant No.RGP-VPP-150
文摘Objective:To correlate the chromatographic and computational method to calculate lipophilicity of selected ginger compounds and to observe the effects of log P on wound healing.Methods:Mixtures of acetonitrile and water with acetonitrile content between 95%and 50%v/v in 5%increments were kept separately in 10 different chromatographic chambers,saturated with solvent for 2 h.Spots were observed under UV light atλ=254 nm p-anisaldehyde used as a spraying reagent Theoretical calculation was done using the Alogps 2.1 online program at www.vcclab.org/lab/alogps.For percentage wound contraction,five groups of animal(mice)(25-30 g)of either sex were selected.Wound were created on dorsal surface of animals using toothed forceps,scalpel and pointed scissors.The wound areas were calculated using vernier caliper.After making wound mice were orally administered 35 mg/kg 6-shogoal,6-gingerol,8-gingerol and 10-gingerol respectively.Croup E as the control group received tap water.Results:The Iipophilicity values determined in thin layer chromatography were correlated with the theoretically calculated various log P by linear regression analysis.Significant correlations were found between log P values calculated by software program and the experimental reversedphase thin-layer chromatography data.Order of wound healing property of ginger compounds is directly dependent on lipophilieity i.e.more lipophilic compound has highest activity.Conclusions:Experimentally determined lipophilieity(R_(MO))values were correlated with log P determined by software's and found satisfactory.Lipophilieity(R_(MO)is a useful parameter for the determination and prediction of biological activity of ginger compounds.
文摘Objectives: To evaluate the barrier function of different skin layers in the process of percutaneous drug absorption. Methods: In vitro permeability via intact or stripped skin of 6 drugs (5-fluorouracil, theo-phylline, hydroquinone, barbital, isosorbide dinitrate and ketoprofen) with a wide span of lipophilicity were investigated in the patch dosage forms. Results: Characteristic parabolic relations was observed between the permeability (Kp, cm/h) of the drugs with different lipophilicity and their LogPc via either intact or stripped skin. However, due to the absence of the stratum corneum, increased Kp ratio for the tested drugs was proportional to their solubility in water other than their LogKp. When isopropyl myristate was used as absorption promoter of the drugs, the parabolic relationship no longer existed. For the intact skin, increase of Kp ratio of the drugs was enhanced resulting from IPM as drug's LogPc decreased. On the other hand, in the case of stripped skin, this enhancement was positively related to the solubility of the drugs in IPM. Conclusion : These data and methods present a novel approach to describe percutaneous drug absorption via damaged or diseased skin.
文摘Reliable prediction of lipophilicity in organic compounds involves molecular descriptors determination. In this work, the lipophilicity of a set of twenty-three molecules has been determined using up to eleven quantum various descriptors calculated by means of quantum chemistry methods. According to Quantitative Structure Property Relationship (QSPR) methods, a first set of fourteen molecules was used as training set whereas a second set of nine molecules was used as test set. Calculations made at AM1 and HF/6-311++G theories levels have led to establish a QSPR relation able to predict molecular lipophilicity with over 95% confidence.
文摘QSAR methodology was used to assess the effects of lipophilicity (logP), molar volume (MV) and polarizability (pl) of the side chains at N2 and C5 of 20 known desoxy anthrapyrazoles on their in vitro anticancer activity expressed as the negative logarithm of the inhibitory concentration of 50% of L1210 murine leukemia cell line (1/logIC50). The main data set shows poor correlations between biological response and the descriptors with exception of MV of the C5 side chain, where a moderate correlation was discerned ( =0.60, n = 18, two outliers). To extract more information regarding mechanism, the main data set was visually classified to three clusters depending on N2 side chain. Cluster 1 containing six 5-substituted 2-[(2-hydroxyethyl) amino] ethyl anthrapyrazoles;cluster 2 contains ten 5-subsitutes 2-(diethyl amino) ethyl anthrapyrazoles and cluster 3 contains four anthrapyrazoles with miscellaneous substituents at both N2 and C5. For cluster 1, MV and pl of C5 show high correlation with biological response (R2’s = 0.75 and 0.72 respectively) while logP gives a weak correlation (R2 = 0.44). For cluster 2, the correlations of logP and pl of C2side chain are higher (=0.66 and 0.62 respectively) compared with MV (=0.16). Cluster 3 shows very poor correlation with all descriptors (~0.3). This indicates mechanistic distinction between the three clusters. Derived descriptors which represent the difference between the descriptors of N2 and C5 side chains where used to explore the presence of interplay between these descriptors in affecting variability of the biological response.
基金supported by the National Natural Science Foundation of China(Nos.52372093 and 52102145)the Key R&D Program of Shaanxi Province(Nos.2023GXLH-045 and 2022SF-168)+4 种基金the Xi’an Programs for Science and Technology Plan(Nos.2020KJRC0090 and 21XJZZ0045)the Opening Project of Shanxi Key Laboratory of Advanced Manufacturing Technology(No.XJZZ202001)the Xi’an Municipal Bureau of Science and Technology(No.21XJZZ0054)the Open Foundation of Key Laboratory of Auxiliary Chemistry and Technology for Chemical Industry,Ministry of Education,Shaanxi University of Science and Technology(No.KFKT2021-01)the Shaanxi Collaborative Innovation Center of Industrial Auxiliary Chemistry and Technology,Shaanxi University of Science and Technology(No.KFKT2021-01).
文摘Melamine sponge is a major concern for oil-water separation due to its lightweight,high porosity(>99%),cost-effectiveness,impressive mechanical properties,and chemical/thermal stability.However,its amphiphilic nature hinders selective oil absorption in water.Recent strategies to enhance hydrophobicity are reviewed,including synthetic methods and materials,with comprehensive explanations of the mechanisms driven by surface energy and roughness.Key performance indicators for MS in oil-water separation,including adsorption capacity,wettability,stability,emulsion separation,reversible wettability switching,flame retardancy,mechanical properties,and recyclability,are thoroughly discussed.In conclusion,this review provides insights into the future potential and direction of functional melamine sponges in oil-water separation.
基金supported by the National Natural Science Foundation of China(No.22101086)Guangzhou Basic and Applied Basic Research Project(No.202201010052)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515140030).
文摘Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.
基金Project supported by the Fund of State Key Laboratory of Elemento-Organic Chemistry, Nankai University
文摘Using methanol-water mixtures as the mobile phase, the chromatographic retention parameters k' and Rf were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and reversed-phase high-performance thin-layer chromatography (RP-HPTLC) for N-(benzothiazol-2-yl)-α-amino alkyl phosphoric diesters and the correlation with lipophilicity parameter (Clog P) was established. Log Kw values obtained from RP-HPLC and Rm values obtained from RP-HPTLC can be used to evaluate the lipophilicity of this kind of compounds. Chromatographic method is a good alternative for lipophilicity measurement.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics.However,it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD.AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD.METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD.The difference in HCC risk between statin users and non-users was calculated among MASLD patients.We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction.RESULTS A total of four studies consisting of 291684 patients were included.MASLD patients on statin therapy had a 60%lower pooled risk of developing HCC compared to the non-statin group[relative risk(RR)=0.40,95%CI:0.31-0.53,I2=16.5%].Patients taking lipophilic statins had a reduced risk of HCC(RR=0.42,95%CI:0.28-0.64),whereas those on hydrophilic statins had not shown the risk reduction(RR=0.57,95%CI:0.27-1.20).The higher(>600)cumulative defined daily doses(cDDD)had a 70%reduced risk of HCC(RR=0.30,95%CI:0.21-0.43).There was a 29%(RR=0.71,95%CI:0.55-0.91)and 43%(RR=0.57,95%CI:0.40-0.82)decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD,respectively.CONCLUSION Statin use lowers the risk of HCC in patients with MASLD.The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.
基金The authors gratefully acknowledge financial support from National Natural Science Foundation of China(81872818)National Key R&D Program of China(2021YFE0115200).
文摘Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
文摘Objective The entorhino-hippocampal pathway is the major excitatory input from neurons of the entorhinal cortex on both ipsilateral and contralateral hippocampus/dentate gyrus. This fiber tract consists of the alvear path, the perforant path and a crossed commissural projection. In this study, the histogenesis and development of the various subsets of the entorhino-hippocampal projection have been investigated. Methods Dil, DiO and fast blue tracing as well as anti-calretinin immunocytochemistry were carried out with prenatal and postnatal rats at different ages. Results The alvear path and the commissural pathway started to develop as early as embryonic day （E） 16, while the first perforant afferents reached the stratum lacunosum-moleculare of the hippocampus at E 17 and the outer molecular layer of dentate gyrus at postnatal day （P） 2, respectively. Retrograde tracing with DiI identified entorhinal neurons in layer II to IV as the origin of entorhino-hippocampal pathway. Furthermore, anti-calretinin immunocytochemistry revealed transitory Cajal- Retzius （CR） cells in the stratum lacunosum-moleculare of the hippocampus from as early as E 16. DiI labeling of entorhinal cortex fibers and combined calretinin-immunocytochemistry showed a close association between CR cells and entorhinal afferents. Conclusion The subsets of entorhino-hippocampal pathway appear in the developmental hippocampus during El6 - P2. The temporal and spatial relationship between CR cell and perforant afferent suggests the role of this cell type as a guiding cue for entorhinal afferents at early cortical development.
文摘Aim To investigate the relationship between pH environment of meptazinolhydrochloride (MEP) and its nasal absorption. Methods In situ nasal peifusion was performed to studythe effect of pH environment on the nasal absorption. Its effect on the transport from nose tobrain was further researched by in vivo experiment. Results In in situ perfusion experiment, thenasal absorption of MEP in basic environment was significantly higher than that in acid condition,but the difference was not observed in in vivo experiment. Conclusion The pH environment ofmeptazinol hydrocloride in formulation cannot be regarded as an important factor influencing nasalabsorption and transport from nose to brain.
文摘Ocular drug delivery is one of the most attention-grabbing and challenging endeavors among the numerous existing drug delivery systems.From a drug delivery point of view,eye is an intricate organ to investigate and explore.In spite of many limitations,advancements have been made with the intention of improving the residence time or permeation of the drug in the ocular region.Poor bioavailability of topically administered drugs is the major issue pertaining to ocular drug delivery.Several efforts have been made towards improving precorneal residence time and corneal penetration,e.g.iontophoresis,prodrugs and ionpairing,etc.Prodrug approach(chemical approach)has been explored by the formulation scientists to optimize the physicochemical and biochemical properties of drug molecules for improving ocular bioavailability.Formulation of ocular prodrugs is a challenging task as they should exhibit optimum chemical stability as well as enzymatic liability so that they are converted into parent drug after administration at the desired pace.This review will encompass the concept of derivatization and recent academic and industrial advancements in the field of ocular prodrugs.The progression in prodrug designing holds a potential future for ophthalmic drug delivery.
基金Project(51174017)supported by the National Natural Science Foundation of China
文摘Corn cob is a naturally renewable material with developed micropore and hydrophobic characteristics, which enables it to show good oil adsorption capacity. In order to improve oil adsorption capacity, corn cob was modified with lauric acid and ethanediol. The structure of raw and modified corn cob was investigated using Fourier transform infrared(FTIR) spectroscopy, scanning electron microscopy(SEM), Brunauer-Emmett-Teller(BET) method, thermogravimetric analysis(TGA) and Ze Ta potential analyzer. The effects of p H level, adsorption time, adsorbent dosage, and initial oil concentration on oil absorbency of corn cob were studied. The results indicate that the modification significantly improved the lipophilicity of corn cob, making the modified corn cob with much better adsorption capacity on oil absorbency. Compared with raw corn cob, the maximum saturated adsorption capacity of modified corn cob is 16.52 mg/g at p H 5, and the increasing percentage is found to be 141%, which indicates that the modification causes a better adsorption capacity for oil removal. In addition, due to high oil adsorption capacity, affordable price and low secondary pollution, the modified corn cob could be considered promising alternative for the traditional oil adsorbent to clean up the emulsified oily water.
基金Pramod Thakare thanks the University of Milan for the Ph.D.fellowship.Giulia Caron,Maura Vallaro and Sonja Visentin acknowledge the financial support from the University of Turin(Ricerca Locale ex-60%,Bando2019).
文摘The first combined experimental and theoretical study on the ionization and lipophilic properties of peptide nucleic acid(PNA)derivatives,including eleven PNA monomers and two PNA decamers,is described.The acidity constants(pKa)of individual acidic and basic centers of PNA monomers were measured by automated potentiometric pH titrations in water/methanol solution,and these values were found to be in agreement with those obtained by MoKa software.These results indicate that single nucleobases do not change their pKa values when included in PNA monomers and oligomers.In addition,immobilized artificial membrane chromatography was employed to evaluate the lipophilic properties of PNA monomers and oligomers,which showed the PNA derivatives had poor affinity towards membrane phospholipids,and confirmed their scarce cell penetrating ability.Overall,our study not only is of potential relevance to evaluate the pharmacokinetic properties of PNA,but also constitutes a reliable basis to properly modify PNA to obtain mimics with enhanced cell penetration properties.
文摘Two acidic carbon materials （H-PRC and HS-C） were used as catalysts for the condensation reaction of methanol with formaldehyde to produce dimethoxymethane （DMM） in aqueous solution （hydrophilic system） and for the etherification of isopentene with methanol to produce tert amyl methyl ether （TAME） in toluene solution （lipophilic system）. Microcalorimetric adsorptions of water and benzene showed that the HS-C was highly hydrophilic without the lipophilicity, while the H-PRC exhibited both the hydrophilicity and lipophilicity. Thus, the HS-C was well dispersed in aqueous solution and difficult to separate from it. On the other hand, the H-PRC was highly active, more active than the acidic resin （D008） and sulfuric acid, for the synthesis of DMM in aqueous solution. The H-PRC was also highly active, more active than the HS-C, for the etherification of isopentene with methanol to produce TAME in toluene solution, probably owing to its amphiphilic surface property as well as its strong surface acidity as measured by the microcalorirnetric adsorption of NH3.
文摘The kinetics of ecotoxicant transport through the membrane was studied. The ecotoxicants studied were pecticides widely used in agriculture: lontrel (clopyralid), sencor (metribuzin), basagran (bentazon), roundup (glyphosate), kusagard (alloxydim sodium), and sethoxydim, as well as lontrel complexes with cobalt and copper. All compounds considered penetrate through the model phosphatidylcholine liposomal membranes. The transfer rate was monitored by fluorescence quenching of ?-ATP inside the liposomes. The mathematical model for the process was proposed, and the mass transfer rates were calculated. The octanol/water partition constants were determined. All the compounds con- sidered were shown to accumulate in the fatty layer. The kinetics of their accumulation was studied, and the rates of accumulation in the nonpolar phase were calculated, which correlate with the complexation constants of the same compounds. Bioaccumulation of the toxicants is caused by the formation of complexes with the fatty phase (lipid part) of the cellular membranes. The toxicants under study transferred into the nonpolar phase with a considerable rate dur- ing the whole observation time, namely, 18 months.
基金This work was performed within the framework of the research project No 172017 supported by the Ministry of Education,Science and Technological development of Serbia.
文摘The retention behavior and lipophilicity parameters of some antiphychotics were determined using reversed-phase thin layer chromatography. Quantitative structure-activity relationships studies have been performed to correlate the molecular characteristics of observed compounds with their retention as well as with their chromatographically determinated lipophilicity parameters. The effect of different organic modifiers (acetone, tetrahydrofuran, and methanol) has been studied. The retention of investigated compounds decreases linearly with increasing concentration of organic modifier. The chemical structures of the antipsychotics have been characterized by molecular descriptors which are calculated from the structure and related to chromatographically determinated lipophilicity parameters by multiple linear regression analysis. This approach gives us the possibility to gain insight into factors responsible for the retention as well as lipophilicity of the investigated set of the compounds. The most prominent factors affecting lipophilicity of the investigated substances are Solubility, Energy of the highest occupied molecular orbital, and Energy of the lowest unoccupied molecular orbital. The obtained models were used for interpretation of the lipophilicity of the investigated compounds. The prediction results are in good agreement with the experimental value. This study provides good information about pharmacologically important physico-chemical parameters of observed antipsychotics relevant to variations in molecular lipophilicity and chromatographic behavior. Established QSAR models could be helpful in design of novel multitarget antipsychotic compounds.
基金Supported by the National Marine Public Welfare Research Project of China(No.201305010)the National Natural Science Foundation of China(No.41106090)+5 种基金the Open Foundation of Key Laboratory of Marine Bio-resources Sustainable Utilization,Chinese Academy of Sciences(No.LMB111003)the Special Fund for Basic Scientific Research of Central Universities(No.21612401)the Natural Science Foundation of Guangdong Province(No.S2011040003113)the National Basic Research Program of China(973 Program)(No.2013CB956503)the Special Project for Science and Technology of Environmental Protection of Zhejiang Province(No.2011A31)the Wenzhou Science and Technology Plan Program(No.S2006A007)
文摘A 12-month program of monitoring potentially toxic microalgae(that produce lipophilic shellfi sh toxins; LSTs) and their toxins in bivalves was conducted from April 2006 to March 2007 in the Nanji Islands, East China Sea. Two Dinophysis species, D. caudata and D. acuminata, were identifi ed, and D. caudat a was found to be the dominant species. D. caudata was detected in water samples between April and June 2006, and between February and March 2007. It reached its highest abundances in May, with a mean abundance of 1.38×10 2 cells/L in surface water and 1.25×10 2 cells/L in bottom water(<10 m deep). The temporal distribution of D. caudata was associated with the occurrence of LSTs in bivalve samples, which mostly occurred at the same time as D. caudata blooms, between April and July 2006. All of the cultured bivalves sampled between April and June were contaminated with LSTs, with an average toxicity of 85 μg okadaic acid(OA) eq./100 g meat, which was four times higher than the Chinese regulatory limit(20 μg OA eq./100 g meat). Ten out of fi fteen wild samples(66.7%) collected during the same period were positive for LSTs, and contained an average LST toxicity of 45 μg OA eq./100 g meat(more than twice the regulatory value). Cultured Patinopecten yessoensis collected on 15 May 2006 had the highest toxicity, 320 μg OA eq./100 g meat, and relatively high toxicities(80 to 160 μg OA eq./100 g meat) were found in bivalves until the end of July.
基金supported by JASSO(Japan Student Services Organization)DPP Grant 2016(Faculty of Forestry,UGM)
文摘The chemical compositions of the dichloromethane extracts of inner and outer barks from six Pinus species（P.elliotii,P.oocarpa,P.caribeae,P.merkusii,P.montezumae,and P.insularis） grown in Indonesia were investigated by GC and GC–MS.Generally,the amounts of extractive contents were higher in the inner bark than in the outer bark except for P.merksuii.Fatty acids,monoterpenes,sesquiterpenes,resin acids,triterpenoids,and steroids were detected and quantified.Inner and outer barks differed not only in content of these compounds but also in their composition.Fatty acids and alcohols were the major classes of lipophilic compounds in the outer bark of P.caribeae, P.insularis,and P.montezumae.Steroids and triterpenoids were the dominant compounds identified in the inner bark of P.elliotii,P.insularis,and P.merkusii.Resin acids were the most abundant group in the inner bark of P.oocarpa whereas monoterpenes and sesquiterpenes were recorded in minor quantities in both bark layers of all species.
