ABSTRACT
Oral exposure to mineral oil may result in a narrow fraction of mineral oil saturated hydrocarbon (MOSH) being retained in tissues. Excess of MOSH hepatic retention may lead to the formation of lipogranuloma caused by predominantly multiring cycloalkanes (naphthenics) in a critical range of C25-C35. Although hepatic lipogranuloma is of low pathological concern, MOSH tissue deposition could be minimized by using an oil of similar quality but devoid of naphthenic structures to decrease hepatic retention. Synthetic Gas to liquid (GTL) oils offer an alternative to petroleum derived mineral oils, because they do not contain naphthenic structures. To demonstrate this point, SD rats were fed either GTL oil (99% iso-alkanes) or naphthenic mineral oil (84% cycloalkanes) at 200 mg/kg bw/day for 90 or 134 days with a recovery group. Liver, fat and mesenteric lymph nodes were analyzed for alkane sub-type levels using Online-HPLC-GC-FID and GCxGC-TOF-MS. Results indicate that at equal external dose, GTL hydrocarbons result in lower tissue levels and more rapid excretion than MOSH. GTL retained hepatic fractions were also qualitatively different than MOSH constituents. Because chemical composition differences, GTL oil show low absorption and tissue retention potential and thus an advantageous alternative to conventional mineral oil.
Subject(s)
Liver , Mineral Oil , Oils , Paraffin , Animals , Cycloparaffins/chemistry , Cycloparaffins/metabolism , Female , Liver/drug effects , Liver/metabolism , Lymph Nodes/metabolism , Mineral Oil/chemistry , Mineral Oil/metabolism , Mineral Oil/pharmacokinetics , Oils/chemistry , Oils/metabolism , Oils/pharmacokinetics , Paraffin/chemistry , Paraffin/metabolism , Paraffin/pharmacokinetics , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
SCOPE: Currently available omega-3 fatty acid supplements do not enrich the docosahexaenoic acid (DHA) of the adult brain because they are absorbed as triacylglycerol, whereas the transporter at the blood brain barrier requires lysophosphatidylcholine (LPC)-DHA. The hypothesis that treatment of krill oil (KO), which contains DHA/eicosapentaenoic acid (EPA) at the SN2 position of phosphatidylcholine, with SN1-specific lipase will generate LPC-DHA/EPA and which can be absorbed intact and transported into the brain, is tested. METHODS: KO and fish oil (FO) are treated with Mucor meihei lipase, incorporated into AIN 93G diet, and fed to 2-month-old mice for 30 days. Fatty acid composition is analyzed by gas chromatography/mass spectroscopy. Brain derived neurotrophic factor (BDNF) is measured by ELISA. RESULTS: Lipase-treated (LT) KO increases brain DHA and EPA, respectively, 5-and 70-fold better than untreated (UT) KO. FO, whether lipase-treated or not, has no effect on brain DHA/EPA. LTKO is also more efficient in enriching liver DHA/EPA, but less efficient than UTKO and FO in enriching adipose tissue and heart. Brain BDNF is significantly increased by LTKO, but only marginally by other preparations. CONCLUSIONS: Pretreatment of dietary KO with lipase enables it to efficiently increase brain DHA/EPA because of the generation of LPC-DHA/EPA.
Subject(s)
Brain/metabolism , Docosahexaenoic Acids/pharmacokinetics , Eicosapentaenoic Acid/pharmacokinetics , Euphausiacea/chemistry , Oils/pharmacokinetics , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Animals , Brain/drug effects , Brain-Derived Neurotrophic Factor/metabolism , Dietary Supplements , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Fatty Acids, Omega-3/metabolism , Fish Oils/chemistry , Fish Oils/pharmacokinetics , Heart/drug effects , Lipase/chemistry , Liver/drug effects , Liver/metabolism , Male , Mice, Inbred C57BL , Oils/chemistry , Tissue DistributionABSTRACT
SCOPE: The docosahexaenoic acid ester of hydroxy linoleic acid (13-DHAHLA) is a bioactive lipid with anti-inflammatory properties from the family of fatty acid esters of hydroxy fatty acids (FAHFA). METHODS AND RESULTS: To explore the biosynthesis of 13-DHAHLA from dietary oils, C57BL/6N mice are gavaged for 8 days with various corn oil/marine oil mixtures containing the same amount of DHA. Plasma levels of omega-3 FAHFAs are influenced by the lipid composition of the mixtures but do not reflect the changes in bioavailability of polyunsaturated fatty acids in plasma. Triacylglycerol-bound DHA and linoleic acid serve as more effective precursors for 13-DHAHLA synthesis than DHA bound in phospholipids or wax esters. Both 13(S)- and 13(R)-DHAHLA inhibit antigen and PGE2 -induced chemotaxis and degranulation of mast cells to a comparable extent and 13(S)-DHAHLA is identified as the predominant isomer in mouse adipose tissue. CONCLUSION: Here, the optimal nutritional source of DHA is identified, which supports production of anti-inflammatory FAHFAs, as triacylglycerol-based marine oil and also reveals a possible role of triacylglycerols in the synthesis of FAHFA lipokines.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Docosahexaenoic Acids/pharmacokinetics , Oils/chemistry , Oils/pharmacokinetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/blood , Aquatic Organisms , Biological Availability , Chemotaxis/drug effects , Fatty Acids, Omega-3/pharmacokinetics , Fatty Acids, Omega-3/pharmacology , Female , Linoleic Acids/chemistry , Male , Mast Cells/drug effects , Mice, Inbred C57BL , Stereoisomerism , Triglycerides/chemistryABSTRACT
This study aimed to develop a supersaturable self-emulsifying drug delivery system (S-SEDDS) of krill oil (KO), a rich source of docosahexaenoic acid and eicosapentaenoic acid (EPA), to improve its hypotriglyceridemic function. S-SEDDS of KO (KO/S-SEDDS) was prepared by the addition of lysolecithin, glycerin, and hydroxypropyl methylcellulose (HPMC). Self-emulsifying drug delivery system of KO (KO/SEDDS) and KO with HPMC (KO/HPMC) were also prepared for comparison purposes. The physicochemical and pharmacokinetic properties of KO samples were characterized, and the hypotriglyceridemic function of KO/S-SEDDS was evaluated. Micronized droplets in KO/SEDDS and KO/S-SEDDS with a mean diameter of ca. 270 nm could be observed in comparison to KO and KO/HPMC. Both KO/HPMC and KO/S-SEDDS tended to enhance the dissolution behavior of KO, and the S-SEDDS formulation improved the dissolution behavior of KO as a result of micronized droplets and the addition of HPMC. KO/S-SEDDS (60 mg of EPA/kg) improved the oral absorption of KO based on the pharmacokinetic profiling of EPA, and repeated oral administration of KO/S-SEDDS (250 mg of KO kg-1 day-1) for 7 days had a potent hypotriglyceridemic effect on rats with corn-oil-induced hypertriglyceridemia compared to orally administered KO. On the basis of these findings, the S-SEDDS approach might be an efficacious dosage option to enhance the nutraceutical properties of KO.
Subject(s)
Drug Delivery Systems , Emulsifying Agents , Euphausiacea/chemistry , Fatty Acids, Omega-3/blood , Oils/pharmacokinetics , Triglycerides/blood , Administration, Oral , Animals , Biological Availability , Emulsions , Fatty Acids, Omega-3/administration & dosage , Male , Oils/administration & dosage , Oils/chemistry , Rats , Rats, Sprague-Dawley , SolubilityABSTRACT
BACKGROUND: Horse oil (HO) has skin barrier restoration and skin-moisturizing effects. Although cream formulations have been used widely and safely, their limited penetration through the stratum corneum is a major obstacle to maximizing the cosmetic efficacy of HO. Therefore, we aimed to encapsulate HO in a cosmetic dissolving microneedle (DMN) for efficient transdermal delivery. METHODS: To overcome these limitations of skin permeation, HO-loaded DMN (HO-DMN) patches were developed and evaluated for their efficacy and safety using in vitro and clinical studies. RESULTS: Despite the lipophilic nature of HO, the HO-DMN patches had a sharp shape and uniform array, with an average length and tip diameter of 388.36 ± 16.73 and 38.54 ± 5.29 µm, respectively. The mechanical strength of the HO-DMN patches was sufficient (fracture force of 0.29 ± 0.01 N), and they could successfully penetrate pig skin. During the 4-week clinical evaluation, HO-DMN patches caused significant improvements in skin and dermal density, skin elasticity, and moisturization. Additionally, a brief safety assessment showed that the HO-DMN patches induced negligible adverse events. CONCLUSION: The HO-DMNs are efficient, safe, and convenient for wide use in cosmetic applications for skin barrier restoration and moisturization.
Subject(s)
Lubricants/administration & dosage , Oils/administration & dosage , Skin Absorption , Skin/drug effects , Administration, Cutaneous , Adult , Animals , Cosmetics/administration & dosage , Cosmetics/isolation & purification , Cosmetics/pharmacokinetics , Drug Delivery Systems , Elasticity/drug effects , Female , Horses , Humans , Lubricants/isolation & purification , Lubricants/pharmacokinetics , Middle Aged , Needles , Oils/isolation & purification , Oils/pharmacokinetics , Skin/metabolism , Swine , Transdermal PatchABSTRACT
Clove is an aromatic plant spice with potent antioxidant and anti-inflammatory activity. Eugenol is the main compound which contributes to such medicinal and nutritional benefits. To date, the formulation of unstable, volatile and poorly water-soluble compounds remains a challenging task. Lipid formulations can be used to improve physicochemical and biopharmaceutical properties of poorly soluble compounds. The aim of this study is to investigate the effects of lipids, such as Gelucire and Compritol on physicochemical properties; stability and in vitro intestinal permeation of spray dried powdered formulations loaded with clove's bioactive compounds. Results showed that eugenol retention in spray-dried powders could be correlated with antioxidant activity and with mass recovery after spray drying. Adding Gelucire but not Compritol to clove extract formulations, improved solubility of spray dried powders. Stability test in high humidity environment (63.5% RH) suggested that formulations including both Gelucire and Compritol were significantly more stable compared to the formulation without any lipid at the two tested temperatures (25 °C and 40 °C). This suggests that lipid additions to clove (Syzygium aromaticum) extract formulations provide protective effects for the spray dried powders in high-humidity environments. In addition, results from in vitro intestinal permeation studies suggested that eugenol uptake, was not being hindered by transporters nor was the absorption being affected by lipid formulations.
Subject(s)
Fats/chemistry , Fats/pharmacokinetics , Gastrointestinal Absorption/drug effects , Oils/chemistry , Oils/pharmacokinetics , Plant Extracts/chemistry , Plant Extracts/pharmacokinetics , Syzygium , Caco-2 Cells , Chemical Phenomena/drug effects , Drug Compounding/methods , Drug Stability , Drug Storage/standards , Excipients/chemistry , Excipients/pharmacokinetics , Humans , Plant Components, Aerial , Plant Extracts/isolation & purification , PowdersABSTRACT
It has been proposed that Emu oil possesses skin permeation-enhancing effect. This study aimed to address its possible penetration enhancement mechanism(s) using IR microscopy, in accordance with LPP theory. The penetration of Emu oil through the layers of human skin was accomplished by monitoring oil-IR characteristic feature at 3006cm-1. The unsaturated components of Emu oil accumulated at about 270µm depth of skin surface. The interaction of Emu oil with lipid and protein constituents of SC was investigated in comparison with a commonly used enhancer, IPM. Inter-sample spectral differences were identified using PCA and linked with possible enhancement mechanisms. Emu oil treatment caused a change in the slope of the right contour of amide I band of the protein spectral range. This was also clear in the second derivative spectra where the emergence of a new shoulder at higher frequency was evident, suggesting disorganization of keratin α-helix structure. This effect could be a result of disruption of some hydrogen bonds in which amide CO and NH groups of keratin are involved. The low intensity of the emerged shoulder is also in agreement with formation of weaker hydrogen bonds. IPM did not affect the protein component. No conclusions regarding the effect of penetration enhancers on the SC lipids were obtained. This was due to the overlap of the endogenous (skin) and exogenous (oil) CH stretching and scissoring frequencies. The SC carbonyl stretching peak disappeared as a result of IPM treatment which may reflect some degree of lipid extraction.
Subject(s)
Oils/analysis , Oils/pharmacokinetics , Skin/chemistry , Skin/metabolism , Spectroscopy, Fourier Transform Infrared/methods , Humans , Lipids/analysis , Lipids/chemistry , Microspectrophotometry/methods , Oils/chemistry , Skin Absorption , SynchrotronsABSTRACT
Paclitaxel is a most widely used anticancer drug with low oral bioavailability, thus it is currently administered via intravenous infusion. DHP107 is a lipid-based paclitaxel formulation that can be administered as an oral solution. In this study, we investigated the mechanism of paclitaxel absorption after oral administration of DHP107 in mice and rats by changing the dosing interval, and evaluated the influence of bile excretion. DHP107 was orally administered to mice at various dosing intervals (2, 4, 8, 12, 24 h) to examine how residual DHP107 affected paclitaxel absorption during subsequent administration. Studies with small-angle X-ray diffraction (SAXS) and cryo-transmission electron microscopy (cryo-TEM) showed that DHP107 formed a lipidic sponge phase after hydration. The AUC values after the second dose were smaller than those after the first dose, which was correlated to the induction of expression of P-gp and CYP in the livers and small intestines from 2 h to 7 d after the first dose. The smaller AUC value observed after the second dose was also attributed to the intestinal adhesion of residual formulation. The adhered DHP107 may have been removed by ingested food, thus resulting in a higher AUC. In ex vivo and in vivo mucoadhesion studies, the formulation adhered to the villi for up to 24 h, and the amount of DHP107 that adhered was approximately half that of monoolein. The paclitaxel absorption after administration of DHP107 was not affected by bile in the cholecystectomy mice. The dosing interval and food intake affect the oral absorption of paclitaxel from DHP107, which forms a mucoadhesive sponge phase after hydration. Bile excretion does not affect the absorption of paclitaxel from DHP107 in vivo.
Subject(s)
Drug Compounding , Intestinal Absorption , Lipids/pharmacokinetics , Oils/pharmacokinetics , Paclitaxel/pharmacokinetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , Administration, Oral , Animals , Bile/metabolism , Biological Availability , Caprylates/chemistry , Cytochrome P-450 CYP2C8/biosynthesis , Cytochrome P-450 CYP3A/biosynthesis , Drug Administration Schedule , Eating , Female , Glycerides/chemistry , Glycerides/pharmacokinetics , Intestine, Small/metabolism , Lipids/chemistry , Liver/metabolism , Mice , Oils/chemistry , Paclitaxel/administration & dosage , Paclitaxel/blood , Paclitaxel/chemistry , Polysorbates/chemistry , Rats , Triglycerides/chemistryABSTRACT
This work aimed at improving the solubility of curcumin by the preparation of spray-dried ternary solid dispersions containing Gelucire®50/13-Aerosil® and quantifying the resulting in vivo oral bioavailability and anti-inflammatory activity. The solid dispersion containing 40% of curcumin was characterised by calorimetry, infrared spectroscopy and X-ray powder diffraction. The solubility and dissolution rate of curcumin in aqueous HCl or phosphate buffer improved up to 3600- and 7.3-fold, respectively. Accelerated stability test demonstrated that the solid dispersion was stable for 9 months. The pharmacokinetic study showed a 5.5-fold increase in curcumin in rat blood plasma when compared to unprocessed curcumin. The solid dispersion also provided enhanced anti-inflammatory activity in rat paw oedema. Finally, the solid dispersion proposed here is a promising way to enhance curcumin bioavailability at an industrial pharmaceutical perspective, since its preparation applies the spray drying, which is an easy to scale up technique. The findings herein stimulate further in vivo evaluations and clinical tests as a cancer and Alzheimer chemoprevention agent.
Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacokinetics , Curcumin/chemistry , Curcumin/pharmacokinetics , Drug Stability , Animals , Anti-Inflammatory Agents/pharmacology , Biological Availability , Chemistry, Pharmaceutical/methods , Curcumin/pharmacology , Fats/chemistry , Fats/pharmacokinetics , Fats/pharmacology , Male , Oils/chemistry , Oils/pharmacokinetics , Oils/pharmacology , Rats , Rats, Wistar , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacokinetics , Silicon Dioxide/pharmacology , Solubility , Technology, Pharmaceutical/methods , X-Ray Diffraction/methodsABSTRACT
In this article, a fluorescence-CT dual-mode nanoprobe is successfully synthesized by making use of distearoylphosphatidylethanolamine-poly(ethylene glycol)-folate (DSPE-PEG2000-FA) and other amphiphilic molecules to coat silver sulfide (Ag2S) quantum dots (QDs) and iodinated oil simultaneously. In vitro experiments show that the fluorescence wavelength of the nanoprobe is 1170 nm in the near infrared-II region. Its size is 139.6 nm, it has good dispersibility, and it has low cellular toxicity at concentrations up to 25 µg mL(-1) Ag. In vivo experiments revealed that the probe has a rather long circulation time (blood half-life of 5.7 hours), and the tissue histopathological tests show that it is not obviously harmful to major organs' normal function. Biochemical analysis (glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels) and blood analysis (white blood cell, red blood cell, hemoglobin and blood platelet counts) reveal that it has little influence on blood within 15 days of administration. When injected into HeLa xenograft nude mice by the tail vein, the probe elicited intensely enhanced fluorescence and X-ray computed tomography (CT) signals in the tumors after 24 hours, and the structure, size and position of tumor tissue were shown clearly. In a word, the probe has good tumor targeting capabilities, and it has significant value in fluorescence-CT dual-mode imaging in vivo.
Subject(s)
Iodine , Neoplasms, Experimental , Oils , Optical Imaging/methods , Quantum Dots , Silver Compounds , Tomography, X-Ray Computed/methods , Animals , Female , HeLa Cells , Humans , Iodine/pharmacokinetics , Iodine/pharmacology , MCF-7 Cells , Male , Mice , Mice, Inbred BALB C , Neoplasms, Experimental/blood , Neoplasms, Experimental/pathology , Oils/pharmacokinetics , Oils/pharmacology , Silver Compounds/pharmacokinetics , Silver Compounds/pharmacologyABSTRACT
BACKGROUND: The subject of oil penetration into the skin is controversially discussed in the scientific literature. METHODS: Confocal Raman microscopy was used for analyzing oil penetration into the skin. The following methods were applied in the study: methods based on tracking specific peaks (method 1), the nonrestricted multiple least square fit (method 2), analyzing the lipid-to-keratin peak ratio using the perpendicular drop-down cutoff procedure (method 3), and the Gaussian function-based deconvolution procedure (method 4). RESULTS: The results obtained using methods 1, 2 and 4 show that the investigated oils do not penetrate deeper than 11 µm into human and porcine skin. Petrolatum has a prominent swelling effect on the stratum corneum (32% in vivo, 28% ex vivo), while the other oils exhibit no significant swelling effect. By using method 3, the penetration profile of oils, and especially of petrolatum, into the skin was interpreted incorrectly for various reasons that are addressed herein below. CONCLUSION: Predominantly remaining in the uppermost corneocyte layers of the stratum corneum, topically applied oils do not reach the viable cells of the stratum spinosum. To exclude any possible mistakes when using the lipid-keratin Raman peak (2,820-3,030 cm-1), the penetration analysis should be performed using the Gaussian function-based deconvolution procedure.
Subject(s)
Oils/pharmacokinetics , Skin/metabolism , Adult , Animals , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Skin Absorption , Spectrum Analysis, Raman , Swine , Young AdultABSTRACT
BACKGROUND: The aim of this review is to summarize the effects of krill oil (KO) or fish oil (FO) on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) incorporation in plasma phospholipids or membrane of red blood cells (RBCs) as shown in human and animal studies. Furthermore, we discuss the findings in relation to the possible different health effects, focusing on lipids, inflammatory markers, cardiovascular disease risk, and biological functions of these two sources of long-chain n-3 polyunsaturated fatty acids (PUFAs). METHODS: A literature search was conducted in PubMed in January 2015. In total, 113 articles were identified, but based on selection criteria, 14 original papers were included in the review. RESULTS: Studies on bioavailability of EPA and DHA from KO and FO in humans and animals are limited and the interpretation is difficult, as different amounts of EPA and DHA have been used, duration of intervention differs, and different study groups have been included. Two human studies--one postprandial study and one intervention study--used the same amount of EPA and DHA from KO or FO, and they both showed that the bioavailability of EPA and DHA from KO seems to be higher than that from FO. Limited effects of KO and FO on lipids and inflammatory markers in human and animal studies were reported. Gene expression data from animal studies showed that FO upregulated the cholesterol synthesis pathway, which was the opposite of the effect mediated by KO. KO also regulated far more metabolic pathways than FO, which may indicate different biological effects of KO and FO. CONCLUSION: There seems to be a difference in bioavailability of EPA and DHA after intake of KO and FO, but more studies are needed before a firm conclusion can be made. It is also necessary to document the beneficial health effects of KO with more human studies and to elucidate if these effects differ from those after regular fish and FO intake.
Subject(s)
Cardiovascular Diseases/prevention & control , Dietary Supplements , Erythrocytes/metabolism , Euphausiacea/chemistry , Fish Oils/pharmacokinetics , Oils/pharmacokinetics , Animals , Biological Availability , Cardiovascular Diseases/etiology , Docosahexaenoic Acids/pharmacokinetics , Eicosapentaenoic Acid/pharmacokinetics , Erythrocyte Membrane/metabolism , Fish Oils/administration & dosage , Fish Oils/blood , Humans , Oils/administration & dosage , Protective Factors , Risk FactorsABSTRACT
The effects of krill oil as an alternative source of n-3 long-chain PUFA have been investigated recently. There are conflicting results from the few available studies comparing fish oil and krill oil. The aim of this study was to compare the bioavailability and metabolic fate (absorption, ß-oxidation and tissue deposition) of n-3 fatty acids originating from krill oil (phospholipid-rich) or fish oil (TAG-rich) in rats of both sexes using the whole-body fatty acid balance method. Sprague-Dawley rats (thirty-six male, thirty-six female) were randomly assigned to be fed either a krill oil diet (EPA+DHA+DPA=1·38 mg/g of diet) or a fish oil diet (EPA+DHA+DPA=1·61 mg/g of diet) to constant ration for 6 weeks. The faeces, whole body and individual tissues were analysed for fatty acid content. Absorption of fatty acids was significantly greater in female rats and was only minimally affected by the oil type. It was estimated that most of EPA (>90 %) and more than half of DHA (>60 %) were ß-oxidised in both diet groups. Most of the DPA was ß-oxidised (57 and 67 % for female and male rats, respectively) in the fish oil group; however, for the krill oil group, the majority of DPA was deposited (82-83 %). There was a significantly greater deposition of DPA and DHA in rats fed krill oil compared with those fed fish oil, not due to a difference in bioavailability (absorption) but rather due to a difference in metabolic fate (anabolism v. catabolism).
Subject(s)
Diet , Docosahexaenoic Acids/metabolism , Eicosapentaenoic Acid/metabolism , Euphausiacea , Fish Oils/metabolism , Oils/metabolism , Animals , Biological Availability , Dietary Fats/metabolism , Dietary Fats/pharmacokinetics , Docosahexaenoic Acids/pharmacokinetics , Eicosapentaenoic Acid/pharmacokinetics , Female , Fish Oils/pharmacokinetics , Fishes , Intestinal Absorption , Male , Oils/pharmacokinetics , Oxidation-Reduction , Phospholipids/metabolism , Random Allocation , Rats, Sprague-Dawley , Sex Factors , Tissue Distribution , Triglycerides/metabolismABSTRACT
BACKGROUND: Krill contains two marine omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly bound in phospholipids. Typical products from krill are krill oil and krill meal. Fish oils contain EPA and DHA predominantly bound in triglycerides. The difference in the chemical binding of EPA and DHA has been suggested to affect their bioavailability, but little is known on bioavailability of EPA and DHA in krill meal. This study was undertaken to compare the acute bioavailability of two krill products, krill oil and krill meal, with fish oil in healthy subjects. METHODS: A randomized, single-dose, single-blind, cross-over, active-reference trial was conducted in 15 subjects, who ingested krill oil, krill meal and fish oil, each containing approx. 1 700 mg EPA and DHA. Fatty acid compositions of plasma triglycerides and phospholipids were measured repeatedly for 72 hours. The primary efficacy analysis was based on the 72 hour incremental area under the curve (iAUC) of EPA and DHA in plasma phospholipid fatty acids. RESULTS: A larger iAUC for EPA and DHA in plasma phospholipid fatty acids was detected after krill oil (mean 89.08±33.36%×h) than after krill meal (mean 44.97±18.07%xh, p<0.001) or after fish oil (mean 59.15±22.22%×h, p=0.003). Mean iAUC's after krill meal and after fish oil were not different. A large inter-individual variability in response was observed. CONCLUSION: EPA and DHA in krill oil had a higher 72-hour bioavailability than in krill meal or fish oil. Our finding that bioavailabilities of EPA and DHA in krill meal and fish oil were not different argues against the interpretation that phospholipids are better absorbed than triglycerides. Longer-term studies using a parameter reflecting tissue fatty acid composition, like erythrocyte EPA plus DHA are needed. TRIAL REGISTRATION: NCT02089165.
Subject(s)
Euphausiacea/chemistry , Fatty Acids/pharmacokinetics , Fish Oils/pharmacokinetics , Animals , Biological Availability , Cross-Over Studies , Docosahexaenoic Acids/blood , Eicosapentaenoic Acid/blood , Female , Humans , Male , Middle Aged , Oils/pharmacokinetics , Phospholipids/blood , Single-Blind Method , Triglycerides/bloodABSTRACT
CONTEXT: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action. OBJECTIVE: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires. MATERIALS AND METHODS: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies. RESULTS AND DISCUSSION: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (Cmax) of 9140.84 ± 614.36 ng/ml at 3 h Tmax and solid dispersion tablets showed Cmax = 11 445.46 ± 149.23 ng/ml at 2 h Tmax. The area under the curve for the control and solid dispersion tablets was 31 495.16 ± 619.92 and 43 126.52 ± 688.89 ng h/ml and the mean resident time was 3.99 and 3.68 h, respectively. CONCLUSION: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug.
Subject(s)
Fats/chemistry , Fats/pharmacokinetics , Flurbiprofen/chemistry , Flurbiprofen/pharmacokinetics , Oils/chemistry , Oils/pharmacokinetics , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Chemistry, Pharmaceutical , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Male , Rabbits , SolubilityABSTRACT
Consumer uses of fuels and lubricants in Europe are subject to the Registration, Evaluation, Authorization and restriction of CHemicals (REACH) legislation. Ten volunteers completed a series of exposure situations to simulate filling a vehicle fuel tank with diesel (ES1 Diesel), adding lubricant to a car engine (two situations, one filling point easier to reach (ES2 Easy) than the other (ES3 Hard)) and lubricating a bicycle chain (ES4 Bike). Dermal exposure to the hands and forearms was assessed using a wipe sampling method. A high proportion of samples was less than the limit of detection (ES1=38%, ES3=60%, ES2 and 4, both 78%). In ES1 Diesel, dermal exposure to the hands and forearms ranged from <0.25 µg/cm(2) to 96.21 µg/cm(2). Significantly higher dermal exposure was observed when a lower level of care was taken to complete the task. In ES2 Easy and ES3 Hard, the hand and forearm results ranged from <0.1 µg/cm(2) to 3.33 µg/cm(2) and from <0.1 µg/cm(2) to 3.54 µg/cm(2), respectively. In ES4 Bike, the hand and forearm exposures ranged from <0.35 µg/cm(2) to 5.25 µg/cm(2). Not all volunteers fully complied with the ES4 instructions, thus highlighting that this situation may have more variability in consumer behaviour. The ratio of the amount measured on the hands and forearms to the amount of product handled for ES1 Diesel, ES2 Easy and ES3 Hard was less than 0.0001%, for ES4 Bike it was 0.04%. Mixed effect models showed that the between and within volunteer variations are small for all except ES1 Diesel, where the within volunteer variation was relatively large (likely due to the few high measurements). This study reports dermal exposure measurement data, which will be of value when updating REACH and other exposure assessments for these, and similar, petroleum products.
Subject(s)
Gasoline/analysis , Lubricants/pharmacokinetics , Oils/pharmacokinetics , Skin Absorption , Adolescent , Adult , Environmental Exposure/analysis , Environmental Monitoring/methods , Female , Forearm , Hand , Humans , Male , Middle Aged , Models, Statistical , Scotland , Surveys and Questionnaires , Volunteers , Young AdultABSTRACT
Caryocar brasiliense, popularly known in Brazil as “pequi”, is a species widely distributed in the Brazilian Cerrado. The seeds are surrounded by a woody endocarp coated with a yellow fleshy mesocarp rich in oil and vitamin A, whose oil has a useful role in the treatment of skin aging and protection of human skin against UV-induced damage and skin hydration. The aim of this study was to evaluate the effect of cosmetic formulations containing pequi oil (Caryocar brasiliense) on skin hydration, after a single application. Hydration effect assessment was performed by applying the formulations under study (Control – no formulation, vehicle, and vehicle + pequi oil) onto forearm skin of 30 human volunteers. Skin capacitance and Transepidermal Water Loss (TEWL) measurements were analyzed before, and at 1, 2 and 3 hours after, a single application. Evaluation results of a single application of the vehicle containing pequi oil showed an increase in stratum corneum water content, indicating a skin moisturizing effect. Results of the evaluation of immediate effects of TEWL demonstrated that the vehicle containing pequi oil significantly increased skin moisture during the 3 h evaluation period. The formulations containing pequi oil showed clinical efficacy, increasing stratum corneum water content and enhancing skin barrier function.
Caryocar brasiliense, popularmente conhecido como “Pequi”, é uma espécie amplamente distribuída no Cerrado Brasileiro. O fruto é composto por sementes com endocarpo rígido e lenhoso, recoberto pelo mesocarpo carnoso, amarelado, rico em óleos e vitamina A, útil na proteção da pele contra raios UV, no tratamento das marcas senis da pele, bem como na hidratação cutânea. O objetivo deste estudo foi avaliar o efeito cosmético de formulações contendo óleo de pequi (Caryocar brasiliense) na hidratação cutânea, após uma única aplicação. Este efeito foi avaliado instrumentalmente através de medidas da capacitância da pele e pela perda de água transepidérmica após 1, 2 e 3 horas de uma única aplicação das formulações em estudo (controle, veículo e veículo + óleo de pequi) na pele do antebraço de 30 voluntários. Por meio das avaliações, a formulação contendo óleo de pequi aumentou o conteúdo de água no estrato córneo após 1, 2 e 3 horas, além de diminuir a perda de água transepidérmica, aumentando, significativamente, a hidratação cutânea durante as 3 horas de avaliação. A formulação contendo óleo de pequi apresentou eficácia clínica, aumentando o conteúdo aquoso do estrato córneo, bem como promovendo o efeito barreira na pele.
Subject(s)
Humans , Oils/pharmacokinetics , Ecosystem , Skin , Cosmetic Technology , Fluid Therapy/classificationABSTRACT
Ceiba pentandra (L.) Gaertn (kapok) is a natural sorbent that exhibits excellent hydrophobic-oleophilic characteristics. The effect of packing density, the oil types and solvent treatment on the sorption characteristics of kapok was studied in a batch system. Oil sorption capacity, retention capacity, entrapment stability and kapok reusability were evaluated. Based on SEM and FTIR analyses, kapok fiber was shown to be a lignocellulosic material with hydrophobic waxy coating over the hollow structures. Higher packing density at 0.08 g/ml showed lower sorption capacity, but higher percentage of dynamic oil retention, with only 1% of oil drained out from the test cell. Kapok remained stable after fifteen cycles of reuse with only 30% of sorption capacity reduction. The oil entrapment stability at 0.08 g/ml packing was high with more than 90% of diesel and used engine oil retained after horizontal shaking. After 8h of chloroform and alkali treatment, 2.1% and 26.3% reduction in sorption capacity were observed, respectively, as compared to the raw kapok. The rigid hollow structure was reduced to flattened-like structure after alkali treatment, though no major structural difference was observed after chloroform treatment. Malaysian kapok has shown great potential as an effective natural oil sorbent, owing to high sorption and retention capacity, structural stability and high reusability.