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Frontiers in Pharmacology 2022Extra virgin olive oil (EVOO) from L. drupes, a cornerstone in the Mediterranean diet, is well known for its nutritional and health properties, especially for...
Extra virgin olive oil (EVOO) from L. drupes, a cornerstone in the Mediterranean diet, is well known for its nutritional and health properties, especially for prevention of cardiovascular diseases and metabolic disorders. Traditionally, beneficial health effects have been largely attributed to the high concentration of monounsaturated fatty acids, and in recent years, these have also been related to other components including oleacein and oleocanthal. Here, we evaluated, for the first time, the antimicrobial activity of different green extra virgin olive oil-based formulations in natural deep eutectic solvents (NaDESs) emerging as powerful and biocompatible solvents. Specifically, the antimicrobial activity of the EVOO extract, as well as purified oleocanthal and oleacein in two NaDESs (choline/glycerol and choline/propylene glycol), against several drug-resistant clinical isolates and standard microbial strains has been evaluated. The main result was the inhibitory activity of the EVOO extract in choline/glycerol as well as oleacein in choline/propylene glycol toward drug-resistant Gram-positive and -negative strains. Specifically, the EVOO extract in choline/glycerol showed the highest antibacterial activity against several clinical strains of , whereas oleacein in choline/propylene glycol was the most effective toward various clinical strains of , , and . In addition, all the formulations tested were effective against spp. In conclusion, our results suggest EVOO-based formulations in NaDESs as an interesting strategy that may help in reducing the risk of development of drug resistance. Under this perspective, the usage of NaDESs for the preparation of new antimicrobial formulations may represent a promising approach.
PubMed: 35548334
DOI: 10.3389/fphar.2022.885735 -
Pharmaceutics Aug 2022In this study, the mucosal permeation and deposition of cannabidiol (CBD) with neat and binary vehicles were investigated. Permeation experiments were performed using...
In this study, the mucosal permeation and deposition of cannabidiol (CBD) with neat and binary vehicles were investigated. Permeation experiments were performed using static diffusion cells coupled with fresh porcine esophageal mucosa. The CBD-vehicle solutions were applied at a fixed dose (~5 mg/cm), and the corresponding permeation parameters were calculated. In neat vehicles, the permeation flux () ranged from 0.89 ± 0.15 to 179.81 ± 23.46 µg·cm·h, while the CBD deposition ranged from 11.5 ± 1.8 to 538.3 ± 105.3 μg·cm. Propylene glycol (PG) and diethylene glycol monoethyl ether (DEGEE) yielded the highest permeability () and CBD deposition, while medium-chain triglycerides (MCT) yielded the lowest and deposition. This was due to the difference in apparent partition coefficient (), which is related to the solubility of CBD in the vehicle. The PG:DEGEE binary vehicle boosted (1.5-1.6 fold) and deposition (2.0-2.7 folds) significantly, compared to neat DEGEE. The combination of DEGEE with MCT dramatically enhanced (11-44 fold) and deposition (1.6-4.7 fold). The addition of lipophilic enhancers, laurocapram, and oleic acid, to PG:DEGEE and DEGEE:MCT vehicles significantly reduced (0.3-0.7 fold) and deposition (0.4-0.8 fold) while nerolidol had no effect. These permeation reductions were found to be related to modification of the and/or diffusivity values. This study provides useful basic information for the development of CBD formulations intended for transmucosal delivery.
PubMed: 36015313
DOI: 10.3390/pharmaceutics14081687 -
The Science of the Total Environment Apr 2022Glycol ethers are organic solvents present in countless products for professional and domestic use. The main toxicological concerns are hematotoxicity, respiratory and...
Glycol ethers are organic solvents present in countless products for professional and domestic use. The main toxicological concerns are hematotoxicity, respiratory and reproductive toxicity. The general population can be exposed when using products containing one or several glycol ethers that evaporate or if sprayed, generate aerosols that can be inhaled. The rate at which glycol ethers enters blood following inhalation exposure are unknown in humans, and chemical risk assessors only rely on animal and in vitro toxicity studies. Propylene glycol monomethyl ether (PGME) and propylene glycol monobutyl ether (PGBE) are two examples of glycol ethers used worldwide. Our study aimed to provide human toxicokinetic data after inhalation exposure of low PGME and PGBE concentrations tested alone or in mixture. Healthy participants (n = 28) were exposed to 35 ppm (131 mg/m) of PGME and 15 ppm (i.e., 83 mg/m) of PGBE for 2 or 6 h. Blood was regularly collected during the exposure sessions. PGME and PGBE were immediately bioavailable in blood during exposure, and the mean absorption rates were up to 13 μg/L/min and 2.45 μg/L/min, respectively. Maximum mean blood concentration (Cmax) was 2.91 mg/L and 0.41 mg/L for PGME and PGBE. The cumulative internal doses over time (area under the curve, AUC) were 11 mg∗h/L and 1.81 mg∗h/L for PGME and PGBE. PGME and PGBE total blood uptake could possibly be higher in physically active individuals, such as workers. We recommend that glycol ethers present on the market undergo toxicological testing with the internal doses we found in our toxicokinetic study.
Topics: Animals; Ethers; Humans; Inhalation Exposure; Propylene Glycol; Solvents; Toxicokinetics
PubMed: 34774961
DOI: 10.1016/j.scitotenv.2021.151637 -
American Journal of Physiology. Lung... Dec 2022The in utero environment is sensitive to toxicant exposure, altering the health and growth of the fetus, and thus sensitive to contaminant exposure. Though recent...
The in utero environment is sensitive to toxicant exposure, altering the health and growth of the fetus, and thus sensitive to contaminant exposure. Though recent clinical data suggest that e-cigarette use does no further harm to birth outcomes than a nicotine patch, this does not account for the effects of vaping during pregnancy on the long-term health of offspring. Pregnant mice were exposed to: ) e-cigarette vapor with nicotine (PV + Nic 2% Nic in 50:50 propylene glycol: vegetable glycerin), ) e-cigarette vapor without nicotine [PV; (50:50 propylene glycol:vegetable glycerin)], or ) HEPA filtered air (FA). Dams were removed from exposure upon giving birth. At 5 mo of age, pulmonary function tests on the offspring revealed female and male mice from the PV group had greater lung stiffness (Ers) and alveolar stiffness (H) compared with the FA group. Furthermore, baseline compliance (Crs) was reduced in female mice from the PV group and in male mice from the PV and PV + Nic groups. Lastly, female mice had decreased forced expiratory volume (FEV0.1) in the PV group, but not in the male groups, compared with the FA group. Lung histology revealed increased collagen deposition around the vessels/airways and in alveolar tissue in PV and PV + Nic groups. Furthermore, goblet hyperplasia was observed in PV male and PV/PV + Nic female mice. Our work shows that in utero exposure to e-cigarette vapor, regardless of nicotine presence, causes lung dysfunction and structural impairments that persist in the offspring to adulthood.
Topics: Pregnancy; Male; Female; Mice; Animals; E-Cigarette Vapor; Nicotine; Electronic Nicotine Delivery Systems; Glycerol; Lung; Propylene Glycol
PubMed: 36218276
DOI: 10.1152/ajplung.00233.2022 -
Nature Communications Oct 2022E-cigarette use has surged, but the long-term health effects remain unknown. E-cigarette aerosols containing nicotine and acrolein, a combustion and e-cigarette...
E-cigarette use has surged, but the long-term health effects remain unknown. E-cigarette aerosols containing nicotine and acrolein, a combustion and e-cigarette byproduct, may impair cardiac electrophysiology through autonomic imbalance. Here we show in mouse electrocardiograms that acute inhalation of e-cigarette aerosols disturbs cardiac conduction, in part through parasympathetic modulation. We demonstrate that, similar to acrolein or combustible cigarette smoke, aerosols from e-cigarette solvents (vegetable glycerin and propylene glycol) induce bradycardia, bradyarrhythmias, and elevations in heart rate variability during inhalation exposure, with inverse post-exposure effects. These effects are slighter with tobacco- or menthol-flavored aerosols containing nicotine, and in female mice. Yet, menthol-flavored and PG aerosols also increase ventricular arrhythmias and augment early ventricular repolarization (J amplitude), while menthol uniquely alters atrial and atrioventricular conduction. Exposure to e-cigarette aerosols from vegetable glycerin and its byproduct, acrolein, diminish heart rate and early repolarization. The pro-arrhythmic effects of solvent aerosols on ventricular repolarization and heart rate variability depend partly on parasympathetic modulation, whereas ventricular arrhythmias positively associate with early repolarization dependent on the presence of nicotine. Our study indicates that chemical constituents of e-cigarettes could contribute to cardiac risk by provoking pro-arrhythmic changes and stimulating autonomic reflexes.
Topics: Animals; Female; Mice; Acrolein; Aerosols; Arrhythmias, Cardiac; Electronic Nicotine Delivery Systems; Glycerol; Menthol; Nicotine; Propylene Glycol; Solvents; Nicotiana; Vegetables
PubMed: 36284091
DOI: 10.1038/s41467-022-33203-1 -
Pharmaceutics Dec 2022Rizatriptan (RZT) is an efficient anti-migraine drug which belongs to the class of selective 5 HT (1B/1D) serotonin receptor agonists. Nevertheless, RZT elicits several...
Rizatriptan (RZT) is an efficient anti-migraine drug which belongs to the class of selective 5 HT (1B/1D) serotonin receptor agonists. Nevertheless, RZT elicits several adverse effects and RZT nasal sprays have a limited half-life, requiring repeated doses that could cause patient noncompliance or harm to the nasopharynx and cilia. The current research aimed to develop orally disintegrating films (ODFs) of RZT employing maltodextrin (MTX) and pullulan (PUL) as film-forming polymers, as well as propylene glycol (PG) as a plasticizer. The ODFs were prepared by solvent casting method (SCM). The technique was optimized using Box-Behnken design (BBD), contemplating the ratios of PUL: MTX and different levels of PG (%) as factor variables. The influence of these factors was systematically analyzed on the selected dependent variables, including film thickness, disintegration time (D-time), folding endurance (FE), tensile strength (TS), percent elongation (%E), moisture content (%), and water uptake (%). In addition, the surface morphology, solid state analysis, drug content uniformity (%), drug release (%), and pH of the RZT-ODFs were also studied. The results demonstrated a satisfactory stable RZT-ODFs formulation that exhibited surface homogeneity and amorphous RZT in films with no discernible interactions between the model drug and polymeric materials. The optimized film showed a rapid D-time of 16 s and remarkable mechanical features. The in vitro dissolution kinetics showed that 100% RZT was released from optimized film compared to 61% RZT released from conventional RZT formulation in the initial 5 min. An animal pharmacokinetic (PK) investigation revealed that RZT-ODFs had a shorter time to achieve peak plasma concentration (T), a higher maximum plasma concentration (C), and area under the curve (AUC) than traditional oral mini capsules. These findings proposed a progressive approach for developing anti-migraine drugs that could be useful in reducing the complications of dysphagia in geriatric and pediatric sufferers.
PubMed: 36559181
DOI: 10.3390/pharmaceutics14122687 -
Frontiers in Nutrition 2022The complexation of protein and polysaccharide has shown considerable potential for the encapsulation of functional food components. In this work, propylene glycol...
Formation mechanism of binary complex based on β-lactoglobulin and propylene glycol alginate with different molecular weights: Structural characterization and delivery of curcumin.
The complexation of protein and polysaccharide has shown considerable potential for the encapsulation of functional food components. In this work, propylene glycol alginate (PGA) molecules with different molecular weights (100, 500, and 2,000 kDa) were prepared through HO oxidation, which were further combined with β-lactoglobulin nanoparticles (β-lgNPs) to form PGA-β-lgNPs complexes for the delivery of curcumin (Cur). Results showed that the depolymerization of PGA molecule was resulted from the breakage of glycosidic bonds in the main chain, and the depolymerization rate of PGA molecule depended on the reaction time, temperature, solution pH and HO concentration. As the increasing molecular weight of PGA, the particle size, zeta-potential and turbidity of the complexes were obviously increased. The formation of PGA/β-lgNPs complexes was mainly driven by non-covalent interaction, including electrostatic gravitational interaction, hydrogen bonding and hydrophobic effect. Interestingly, the difference in the molecular weight of PGA also led to significantly differences in the micro-morphology of the complexes, as PGA with a high molecular weight (2,000 kDa) generated the formation of a "fruit-tree" shaped structure, whereas PGA with relatively low molecular weight (100 and 500 kDa) led to spherical particles with a "core-shell" structure. In addition, the incorporation of PGA molecules into β-lgNPs dispersion also contributed to the improvement in the encapsulation efficiency of Cur as well as physicochemical stability of β-lgNPs, and PGA with a higher molecular weight was confirmed with a better effect. Findings in the current work may help to further understand the effect of molecular weight of polysaccharide on the physical and structural properties as well as effectiveness as delivery systems of polysaccharide-protein complexes, providing for the possibility for the design and development of more efficient carriers for bioactive compounds in food system.
PubMed: 35928836
DOI: 10.3389/fnut.2022.965600 -
BioMed Research International 2022Plumbagin, a bioactive naphthoquinone, has demonstrated potent antitumor potential. However, plumbagin is a sparingly water-soluble compound; therefore, clinical...
Plumbagin, a bioactive naphthoquinone, has demonstrated potent antitumor potential. However, plumbagin is a sparingly water-soluble compound; therefore, clinical translation requires and will be facilitated by the development of a new pharmaceutical formulation. We have generated an oil-in-water nanoemulsion formulation of plumbagin using a low-energy spontaneous emulsification process with propylene glycol caprylate (Capryol 90) as an oil phase and Labrasol/Kolliphor RH40 as surfactant and cosurfactant excipients. Formulation studies using Capryol 90/Labrasol/Kolliphor RH40 components, based on pseudoternary diagram and analysis of particle size distribution and polydispersity determined by dynamic light scattering (DLS), identified an optimized composition of excipients for nanoparticle formulation. The nanoemulsion loaded with plumbagin as an active pharmaceutical ingredient had an average hydrodynamic diameter of 30.9 nm with narrow polydispersity. The nanoemulsion exhibited long-term stability, as well as good retention of particle size in simulated physiological environments. Furthermore, plumbagin-loaded nanoemulsion showed an augmented cytotoxicity against prostate cancer cells PTEN-P2 in comparison to free drug. In conclusion, we generated a formulation of plumbagin with high loading drug capacity, robust stability, and scalable production. Novel Capryol 90-based nanoemulsion formulation of plumbagin demonstrated antiproliferative activity against prostate cancer cells, warranting thus further pharmaceutical development.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Carriers; Emulsions; Male; Mice; Nanoparticles; Naphthoquinones; Propylene Glycol; Prostatic Neoplasms
PubMed: 35047632
DOI: 10.1155/2022/3549061 -
Materials (Basel, Switzerland) May 2022Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting....
Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40-45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box-Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF's was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0-t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.
PubMed: 35629620
DOI: 10.3390/ma15103591 -
Polymers Aug 2021Polymethacrylic molecular brushes with oligo(ethylene glycol)-block-oligo(propylene glycol) side chains were investigated by static and dynamic light scattering and...
Polymethacrylic molecular brushes with oligo(ethylene glycol)-block-oligo(propylene glycol) side chains were investigated by static and dynamic light scattering and viscometry. The solvents used were acetonitrile, tetrahydrofuran, chloroform, and water. The grafted copolymers were molecularly dispersed and dissolved in tetrahydrofuran and acetonitrile. In these solvents, the molar masses of copolymers were determined. In thermodynamically good solvents, namely tetrahydrofuran and acetonitrile, investigated copolymers have a high intramolecular density and the shape of their molecules resembles a star-shaped macromolecule. In chloroform and water, the micelle-like aggregates were formed. Critical micelle concentrations decreased with the lengthening of the hydrophobic block. Molecular brushes demonstrated thermosensitive behavior in aqueous solutions. The phase separation temperatures reduced with an increase in the content of the oligo(propylene glycol) block.
PubMed: 34451252
DOI: 10.3390/polym13162715