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Current Pharmaceutical Design 2024Transdermal delivery of highly lipophilic molecules is challenging due to the strong barrier function of the skin. Vesicles with penetration enhancers are safe and...
BACKGROUND
Transdermal delivery of highly lipophilic molecules is challenging due to the strong barrier function of the skin. Vesicles with penetration enhancers are safe and efficient systems that could improve the transdermal delivery of non-psychoactive cannabinoids such as cannabidiol and desoxy-cannabidiol. In the last decades, research interest in desoxy-cannabidiol as a potent drug with anti-nociceptive properties has risen. Still, its scarce market availability poses a limit for both research and clinical applications. Therefore, it is necessary to improve the synthesis to produce sufficient amounts of desoxy-cannabidiol. Moreover, also the formulation aspects for this drug are challenging and require to be addressed to meet an efficient delivery to the patients.
OBJECTIVE
This work aimed to develop innovative phospholipid-based vesicles with propylene glycol (PG), oleic acid (OA), or limonene as edge activators, for the transdermal delivery of highly lipophilic drugs such as non-psychoactive cannabinoids. In particular, desoxy-cannabidiol was selected thanks to its anti-nociceptive activity, and its synthesis was improved enhancing the stereoselectivity of its synthon's production.
METHODS
Desoxy-cannabidiol was synthesized by Lewis acid-mediated condensation of p-mentha-2,8-dien- 1-ol and m-pentylphenol, improving the stereoselectivity of the first synthon's production. Transethosomes containing 20-50% w/w PG, 0.4-0.8% w/w OA, or 0.1-1% w/w limonene were optimized and loaded with cannabidiol or desoxy-cannabidiol (0.07-0.8% w/w, 0.6-7.0 mg/mL). studies were performed to assess both the skin permeation and accumulation of the cannabinoids, as well as the penetration depth of fluorescein- loaded systems used as models.
RESULTS
An enantioselective bromination was added to the pathway, thus raising the production yield of pmentha- 2,8-dien-1-ol to 81% against 35%, and the overall yield of desoxy-cannabidiol synthesis from 12% to 48%. Optimized transethosomes containing 0.6 mg/mL cannabinoids were prepared with 1:10 PG:lipid weight ratio, 0.54 OA:lipid molar ratio, and 0.3 limonene:lipid molar ratio, showing good nanometric size (208 ± 20.8 nm - 321 ± 26.3 nm) and entrapment efficiency (> 80%). tests showed both improved skin permeation rates of cannabinoids (up to 21.32 ± 4.27 μg/cm2 cannabidiol), and skin penetration (depth of fluorescein up to 240 μm, with PG).
CONCLUSION
Desoxy-cannabidiol was successfully produced at high yields, and formulated into transethosomes optimized for transdermal delivery. Loaded vesicles showed improved skin penetration of desoxy-cannabidiol, cannabidiol and a lipophilic probe. These results suggest the potential of these carriers for the transdermal delivery of highly lipophilic drugs.
Topics: Administration, Cutaneous; Cannabinoids; Animals; Skin Absorption; Drug Delivery Systems; Skin; Humans; Cannabidiol; Rats; Male; Molecular Structure
PubMed: 38482628
DOI: 10.2174/0113816128289593240226071813 -
ACS Omega Aug 2023Multiwalled carbon nanotubes (MWCNTs) were employed as added particles for nanofluids in this practical investigation. To identify the most appropriate nanofluid for...
Multiwalled carbon nanotubes (MWCNTs) were employed as added particles for nanofluids in this practical investigation. To identify the most appropriate nanofluid for cooling PVT systems that are functional in the extreme summer environment of Baghdad, the parameters of base fluid, surfactant, and sonication time used for mixing were examined. Water was chosen as the base fluid instead of other potential candidates such as ethylene glycol (EG), propylene glycol (PG), and heat transfer oil (HTO). Thermal conductivity and stability were important thermophysical qualities that were impacted by the chosen parameters. The nanofluid tested in Baghdad city (consisting of 0.5% MWCNTs, water, and CTAB with a sonication period of three and a quarter hours) resulted in a 119.5, 308, and 210% enhancement of thermal conductivity (TC) for water compared with EG, PG, and oil, respectively. In addition, the nanofluid-cooled PVT system had an electrical efficiency that was 88.85% higher than standalone PV technology and 44% higher than water-cooled PVT systems. Moreover, the thermal efficiency of the nanofluid-cooled PVT system was 20% higher than the water-cooled PVT system. Finally, the nanofluid-cooled PVT system displayed the least decrease in electrical efficiency and a greater thermal efficiency even when the PV panel was at its hottest at noon.
PubMed: 37636957
DOI: 10.1021/acsomega.2c07226 -
Frontiers in Veterinary Science 2023Topical wound treatments rely on carrier formulations with little to no biological impact. The potential for a common vehicle, a propylene glycol (PG) gel, to affect...
INTRODUCTION
Topical wound treatments rely on carrier formulations with little to no biological impact. The potential for a common vehicle, a propylene glycol (PG) gel, to affect wound healing measures including microbiota is not known. Microbiome characterization, based on next generation sequencing methods is typically performed on tissue or directly obtained wound fluid samples. The utility for primary wound dressings to characterize equine wound microbiota in the context of topical treatments is currently unknown. This investigation reports the topical effect of an 80% PG based gel on wound healing and microbiota in wound dressings.
METHODS
Experiments were performed in six mature horses utilizing a surgical, distal limb wound model, histology of sequential wound biopsies, photographic wound measurements and microbiota profiling via 16s rRNA sequencing of wound dressing samples. Experimental wounds were surveyed for 42 days and either treated (Day 7, 14, 21 and 28; at 0.03 ml/cm) or unexposed to the PG gel. Wound surface area, relative and absolute microbial abundances, diversity indices and histologic parameters were analyzed in the context of the experimental group (treatment; control) using qualitative or quantitative methods depending on data characteristics.
RESULTS
Compared to controls, treatment slowed the wound healing rate (17.17 ± 4.27 vs. 18.56 ± 6.3 mm/day), delayed the temporal decline of polymorphonucleated cells in wound beds and operational taxonomic units (OTU) in wound dressings and lowered alpha-diversity indices for microbiota in primary wound dressing. Relative abundances of OTUs were in line with those previously reported for equine wounds. Clinical outcomes 42 days post wounding were considered similar irrespective of PG gel exposure.
DISCUSSION
Results highlight the potential for vehicle exposure to alter relevant wound outcome measures, imposing the need for stringent experimental control measures. Primary wound dressings may represent an alternate sample source for characterization of the wound microbiome alleviating the need for additional interventions. Further studies are warranted to contrast the microbiome in wound dressings against that present on wound surfaces to conclude on the validity of this approach.
PubMed: 38155761
DOI: 10.3389/fvets.2023.1294021 -
The Journal of Chemical Physics Apr 2024In the interstellar medium, diols and other prebiotic molecules adsorb onto icy mantles surrounding dust grains. Water in the ice may affect the reactivity and...
In the interstellar medium, diols and other prebiotic molecules adsorb onto icy mantles surrounding dust grains. Water in the ice may affect the reactivity and photoionization of these diols. Ethylene glycol (EG), 1,2-propylene glycol, and 1,3-propylene glycol clusters with water clusters were used as a proxy to study these interactions. The diol-water clusters were generated in a continuous supersonic molecular beam, photoionized by synchrotron-based vacuum ultraviolet light from the Advanced Light Source, and subsequently detected by reflectron time-of-flight mass spectrometry. The appearance energies for the detected clusters were determined from the mass spectra, collected at increasing photon energy. Clusters of both diol fragments and unfragmented diols with water were detected. The lowest energy geometry optimized conformers for the observed EG-water clusters and EG fragment-water clusters have been visualized using density functional theory (DFT), providing insight into hydrogen bonding networks and how these affect fragmentation and appearance energy. As the number of water molecules clustered around EG fragments (m/z 31 and 32) increased, the appearance energy for the cluster decreased, indicating a stabilization by water. This trend was supported by DFT calculations. Fragment clusters from 1,2-propylene glycol exhibited a similar trend, but with a smaller energy decrease, and no trend was observed from 1,3-propylene glycol. We discuss and suggest that the reactivity and photoionization of diols in the presence of water depend on the size of the diol, the location of the hydroxyl group, and the number of waters clustered around the diol.
PubMed: 38591680
DOI: 10.1063/5.0198162 -
Ecotoxicology and Environmental Safety Feb 2024Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have...
Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.
Topics: Male; Female; Rats; Animals; Glycerol; Electronic Nicotine Delivery Systems; Vegetables; Multiomics; Proteomics; Propylene Glycol; Solvents; Aerosols
PubMed: 38277972
DOI: 10.1016/j.ecoenv.2024.116002 -
Animal Reproduction Science Dec 2023Oxidative status is important in reproductive performance and using two natural antioxidants is more beneficial than one in nulliparous rabbits. The goal, effect of...
Oxidative status is important in reproductive performance and using two natural antioxidants is more beneficial than one in nulliparous rabbits. The goal, effect of vitamin E (VitE), D-limonene (DL), and VitE+DL on maternal LBW (MLBW), conception (CR), pregnancy (PR), and kindling rates (KR), gestation length (GL), total litter size at birth (TLSB) and weaning (TLSW), live kits at birth (LKB) and weaning (LKW), dead kits at birth (DKB) and weaning (DKW), kits mortality rate at weaning (KMRW), Kit weight at birth (KWB) and weaning (KWW), total kit weight at birth (TKWB) and weaning (TKWW), and concentrations of progesterone (P4) and Malondialdehyde (MDA), during first two pregnancies. A total of 24 healthy female WNZ rabbits were randomly selected and assigned into four groups (6/each). Control (animals injected with 1.0 mL propylene glycol), VitE (60 mg IM injection/animal, 2X/week pre-mating and 3X post-mating until mid-pregnancy, DL (20 mg IM injection/animal, 2X/week pre-mating and 1X at mating, and VitE+DL (IM injection/animal with the same doses and times applied in VitE and DL groups. All animals were treated during 1st pregnancy only. The results confirmed that animals treated with VitE+DL gained significant maternal LBW in 1st pregnancy, reduced dead kit number at birth and kit mortality rate at weaning, increased live kits and total kit weight at birth and weaning in the two pregnancies, and also increased significantly kit weight at birth and weaning in the treatments than controls in the two pregnancies, and DL was greater in 1st pregnancy. Progesterone concentrations in mid-pregnancy rose significantly in VitE+DL during 1st pregnancy and DL in 2nd pregnancy. Malondialdehyde concentrations dropped significantly in VitE and VitE+DL in mid-pregnancy in the two pregnancies. Eventually, the integration of VitE and DL displayed their unique properties for improving productive and reproductive performance in nulliparous rabbits.
Topics: Animals; Female; Pregnancy; Rabbits; Birth Weight; Limonene; Litter Size; Malondialdehyde; Progesterone; Reproduction; Vitamin E; Weaning
PubMed: 37989002
DOI: 10.1016/j.anireprosci.2023.107378 -
Scientific Reports Jun 2024The use of deicers in urban areas, on runways and aircrafts has raised concerns about their environmental impact. Understanding the ice-melting mechanism is crucial for...
The use of deicers in urban areas, on runways and aircrafts has raised concerns about their environmental impact. Understanding the ice-melting mechanism is crucial for developing environmentally friendly deicers, yet it remains challenging. This study employs machine learning to investigate the ice penetration capacity (IPC) of 21 salts and 16 organic solvents as deicers. Relationships between their IPC and various physical properties were analysed using extreme gradient boosting (XGBoost) and Shapley additive explanation (SHAP). Three key ice-melting mechanisms were identified: (1) freezing-point depression, (2) interactions between deicers and HO molecules and (3) infiltration of ions into ice crystals. SHAP analysis revealed different ice-melting factors and mechanisms for salts and organic solvents, suggesting a potential advantage in combining the two. A mixture of propylene glycol (PG) and sodium formate demonstrated superior environmental impact and IPC. The PG and sodium formate mixture exhibited higher IPC when compared to six commercially available deicers, offering promise for sustainable deicing applications. This study provides valuable insights into the ice-melting process and proposes an effective, environmentally friendly deicer that combines the strengths of organic solvents and salts, paving the way for more sustainable practices in deicing.
PubMed: 38849379
DOI: 10.1038/s41598-024-62942-y -
Soft Matter Nov 2023Acrylamide (AM)-induced enhanced solubilization of poly(ethylene oxide)--poly(propylene oxide)--poly(ethylene oxide) (PEO-PPO-PEO) has been phenomenologically reported...
Acrylamide (AM)-induced enhanced solubilization of poly(ethylene oxide)--poly(propylene oxide)--poly(ethylene oxide) (PEO-PPO-PEO) has been phenomenologically reported in a previous study. However, little is known about its mechanism. In this study, poly(propylene glycol) (PPG) serves as a model system to clarify this enhanced solubilization phenomenon, driven by two specific reasons. First, it helps eliminate any interference from PEO segments. Second, the liquid state of low molecular weight PPG proves advantageous for characterizing molecular interactions. The phenomenon of AM-induced enhanced solubilization has been conclusively demonstrated in the PPG system for the first time. Addition of AM consistently raises the cloud point of PPG aqueous solution. Subsequently, the structure and molecular interactions within the PPG/AM aqueous solution were investigated. Notably, there is no robust association or hydrogen bond between PPG and AM molecules; instead, only van der Waals forces are found to be at play. A model has been constructed, grounded in the contacts between PPG and the solvent during the coil-to-globule transition, to better understand the observed impact of AM on the clouding behavior of PPG aqueous solutions. The mechanism behind the enhanced solubilization has been ascribed to AM's ability to contact with PPG during the temperature-induced dehydration process, thereby assisting in sustaining the PPG's dissolved state.
PubMed: 37987245
DOI: 10.1039/d3sm01362f -
EMBO Molecular Medicine Dec 2023Aerosol transmission remains a major challenge for the control of respiratory viruses. To date, prevention strategies include masks, vaccinations, physical distancing,...
Aerosol transmission remains a major challenge for the control of respiratory viruses. To date, prevention strategies include masks, vaccinations, physical distancing, travel restrictions, and lockdowns. Such measures are effective but come with heavy societal burdens and rely on public compliance. Additionally, most are simply not suitable as long-term measures. Other strategies evolve around the concept of improved indoor air quality and involve ventilation, relative humidity (RH) control, and air filtration. Unfortunately, natural ventilation increases exposure to airborne pollutants and vector-borne diseases, and incurs substantial energy losses in colder months. Mechanical ventilation concepts, including regular air changes and filtration, are effective but costly, and often require expensive engineering solutions and widespread renovations. Alternative options to reduce the spread of emerging and seasonal infections are sorely needed. In this issue of EMBO Molecular Medicine, Styles et al (2023) describe the use of propylene glycol (PG) to inactivate infectious bioaerosols and virus-containing droplets deposited on surfaces.
Topics: Humans; Air Pollution, Indoor; Communicable Diseases; Ventilation; Antiviral Agents
PubMed: 37969101
DOI: 10.15252/emmm.202318710 -
Veterinary Anaesthesia and Analgesia Sep 2023To determine whether L-carvone increases the voltage threshold response to a noxious electrical stimulus in sheep.
OBJECTIVE
To determine whether L-carvone increases the voltage threshold response to a noxious electrical stimulus in sheep.
STUDY DESIGN
Prospective, blinded, randomized, crossover experimental study.
ANIMALS
A group of six healthy adult sheep.
METHODS
Sheep were instrumented with cranial dorsothoracic subcutaneous copper electrodes. A stimulator delivered a 10 ms square-wave stimulus at 50 pps starting at 0.1 V with a 0.2 V second ramp. The stimulus stopped once two observers who were blinded to treatment noted a behavioral pain response or when a 15 V cut-off was reached. Next, 0.15 mL kg of either a 50% L-carvone solution or a saline-vehicle control was administered intramuscularly, and electrical threshold responses were measured every 5-15 minutes over a 6 hour period using methods identical to the baseline. One week following the first treatment (L-carvone or control), sheep were studied using identical methods with the second treatment (control or L-carvone). Drug and time effects were evaluated using a two-way repeated measures analysis of variance, and pairwise comparisons were evaluated with Holm-Sidák tests with values of p < 0.05 considered significant.
RESULTS
L-carvone significantly increased voltage threshold responses for most time points up to 75 minutes compared with baseline and with saline control. The last time point with a significantly different response between L-carvone and saline treatments was 5 hours after drug administration. The saline-vehicle control decreased voltage threshold responses at several time points after 3 hours.
CONCLUSIONS AND CLINICAL RELEVANCE
Intramuscular L-carvone is analgesic in sheep, although the ethanol-propylene glycol vehicle may cause mild hyperalgesia. This study demonstrates that a food-derived compound can be used to relieve pain in a food-producing animal.
Topics: Animals; Analgesics; Pain; Prospective Studies; Sheep; Terpenes
PubMed: 37500407
DOI: 10.1016/j.vaa.2023.06.004