-
BMC Veterinary Research May 2024Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g.,... (Comparative Study)
Comparative Study
Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels.
BACKGROUND
Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties against melanomas and other tumors and have already shown good safety and tolerability in vivo. In this study, BA and NVX-207 were tested for their permeation potential into equine skin in vitro in Franz-type diffusion cell (FDC) experiments after incubation of 5 min, 30 min and 24 h, aiming to use these formulations for prospective in vivo studies as a treatment for early melanoma stages. Potent permeation was defined as reaching or exceeding the half maximal inhibitory concentrations (IC) of BA or NVX-207 for equine melanoma cells in equine skin samples. The active ingredients were either dissolved in a microemulsion (ME) or in a microemulsion gel (MEG). All of the formulations were transdermally applied but the oil-in-water microemulsion was administered with a novel oxygen flow-assisted (OFA) applicator (DERMADROP TDA).
RESULTS
All tested formulations exceeded the IC values for equine melanoma cells for BA and NVX-207 in equine skin samples, independently of the incubation time NVX-207 applied with the OFA applicator showed a significant time-dependent accumulation and depot-effect in the skin after 30 min and 24 h (P < 0.05).
CONCLUSIONS
All tested substances showed promising results. Additionally, OFA administration showed a significant accumulation of NVX-207 after 30 min and 24 h of incubation. Further in vivo trials with OFA application are recommended.
Topics: Animals; Horses; Betulinic Acid; Pentacyclic Triterpenes; Triterpenes; Administration, Cutaneous; Emulsions; Skin; Drug Delivery Systems; Gels; Melanoma; Oxygen; Skin Absorption; Horse Diseases; Propanolamines
PubMed: 38755639
DOI: 10.1186/s12917-024-04064-1 -
BMC Chemistry May 2024Brucellosis poses a significant challenge in the medical field as a systemic infection with a propensity for relapse. This study presented a novel approach to...
Brucellosis poses a significant challenge in the medical field as a systemic infection with a propensity for relapse. This study presented a novel approach to brucellosis treatment, enhancing the efficacy of doxycycline and rifampicin through the use of poly (lactic-co-glycolic) acid coupled with cadmium-telluride quantum dots (Dox-Rif-PLGA@CdTe). The double emulsion solvent evaporation method was employed to prepare Dox-Rif-PLGA@CdTe. The study scrutinized the physicochemical attributes of these nanoparticles. The impact of antibiotic-loaded nanoparticles on Brucella melitensis was evaluated through well diffusion, minimum inhibitory concentration (MIC), and cell culture. The chemical analysis results demonstrated a possibility of chemical reactions occurring among the constituents of nanoparticles. Assessments using the well diffusion and MIC methods indicated that the impact of free drugs and nanoparticles on bacteria was equivalent. However, the drug-loaded nanoparticles significantly decreased the colony-forming units (CFUs) within the cell lines compared to free drugs. In conclusion, the synthesis of nanoparticles adhered to environmentally friendly practices and demonstrated safety. The sustained drug release over 100 h facilitated drug accumulation at the bacterial site, resulting in a heightened therapeutic effect on B. melitensis and improved outcomes in brucellosis treatment. The application of these synthesized nanodrugs exhibited promising therapeutic potential.
PubMed: 38750589
DOI: 10.1186/s13065-024-01200-8 -
Biomedicine & Pharmacotherapy =... Jun 2024Connective tissue growth factor (CTGF) holds great promise for enhancing the wound healing process; however, its clinical application is hindered by its low stability...
Connective tissue growth factor (CTGF) holds great promise for enhancing the wound healing process; however, its clinical application is hindered by its low stability and the challenge of maintaining its effective concentration at the wound site. Herein, we developed novel double-emulsion alginate (Alg) and heparin-mimetic alginate sulfate (AlgSulf)/polycaprolactone (PCL) nanoparticles (NPs) for controlled CTGF delivery to promote accelerated wound healing. The NPs' physicochemical properties, cytocompatibility, and wound healing activity were assessed on immortalized human keratinocytes (HaCaT), primary human dermal fibroblasts (HDF), and a murine cutaneous wound model. The synthesized NPs had a minimum hydrodynamic size of 200.25 nm. Treatment of HaCaT and HDF cells with Alg and AlgSulf/PCL NPs did not show any toxicity when used at concentrations <50 µg/mL for up to 72 h. Moreover, the NPs' size was not affected by elevated temperatures, acidic pH, or the presence of a protein-rich medium. The NPs have slow lysozyme-mediated degradation implying that they have an extended tissue retention time. Furthermore, we found that treatment of HaCaT and HDF cells with CTGF-loaded Alg and AlgSulf/PCL NPs, respectively, induced rapid cell migration (76.12% and 79.49%, P<0.05). Finally, in vivo studies showed that CTGF-loaded Alg and AlgSulf/PCL NPs result in the fastest and highest wound closure at the early and late stages of wound healing, respectively (36.49%, P<0.001 on day 1; 90.45%, P<0.05 on day 10), outperforming free CTGF. Double-emulsion NPs based on Alg or AlgSulf represent a viable strategy for delivering heparin-binding GF and other therapeutics, potentially aiding various disease treatments.
Topics: Wound Healing; Alginates; Polyesters; Humans; Connective Tissue Growth Factor; Animals; Nanoparticles; Mice; HaCaT Cells; Fibroblasts; Male; Drug Carriers; Cell Line; Drug Delivery Systems; Keratinocytes; Particle Size; Sulfates
PubMed: 38749174
DOI: 10.1016/j.biopha.2024.116750 -
Anais Da Academia Brasileira de Ciencias 2024Bioactive substances can be found in wine lees, a waste from the winemaking industry. This work developed two formulations, a nanoemulsion with coconut oil (NE-OC) and a...
Bioactive substances can be found in wine lees, a waste from the winemaking industry. This work developed two formulations, a nanoemulsion with coconut oil (NE-OC) and a nanoemulsion with coconut oil and 0.5% of wine lees extract (NE-OC-Ext), to investigate their effect on untreated, bleached, and bleached-colored hair. The oil-in-water (O/W) nanoemulsions were prepared with coconut oil, TweenTM 80, SpanTM 80, AristoflexTM AVC, Conserve NovaMit MFTM, wine lees extract, and deionized water. The hydration measurements were carried out using a Corneometer® CM 825 with the capacitance method. Scanning electron microscopy (SEM) was used to characterize the effect of formulations on hair fibers. Differential Thermal Analysis (DTA) was to assess the thermal stability and compatibility of wine lees and coconut oil in formulations. Compared to NE-OC, NE-OC-Ext showed a greater hydration effect on bleached-colored hair. DTA showed that NE-OC-Ext presented a smaller number of exothermic degradation events than those of NE-OC, suggesting good interaction and compatibility of the wine lees extract in this formulation. This study highlights the value of wine lees, a residue from the winemaking process, and its possibility of use as raw material for the cosmetic hair industry since it shows a greater moisturizing potential in colored hair.
Topics: Wine; Emulsions; Coconut Oil; Microscopy, Electron, Scanning; Hair; Humans; Green Chemistry Technology
PubMed: 38747835
DOI: 10.1590/0001-3765202420230373 -
BioRxiv : the Preprint Server For... May 2024Lipids are an important component of food and oral drug formulations. Upon release into gastrointestinal fluids, triglycerides, common components of foods and drug...
Lipids are an important component of food and oral drug formulations. Upon release into gastrointestinal fluids, triglycerides, common components of foods and drug delivery systems, form emulsions and are digested into simpler amphiphilic lipids (e.g., fatty acids) that can associate with intestinal bile micelles and impact their drug solubilization capacity. Digestion of triglycerides is dynamic and dependent on lipid quantity and type, and quantities of other components in the intestinal environment (e.g., bile salts, lipases). The ability to predict lipid digestion kinetics in the intestine could enhance understanding of lipid impact on the fate of co-administered compounds (e.g., drugs, nutrients). In this study, we present a kinetic model that can predict the lipolysis of emulsions of triolein, a model long-chain triglyceride, as a function of triglyceride amount, droplet size, and quantity of pancreatic lipase in an intestinal environment containing bile micelles. The model is based on a Ping Pong Bi Bi mechanism coupled with quantitative analysis of partitioning of lipolysis products in colloids, including bile micelles, in solution. The agreement of lipolysis model predictions with experimental data suggests that the mechanism and proposed assumptions adequately represent triglyceride digestion in a simulated intestinal environment. In addition, we demonstrate the value of such a model over simpler, semi-mechanistic models reported in the literature. This lipolysis framework can serve as a basis for modeling digestion kinetics of different classes of triglycerides and other complex lipids as relevant in food and drug delivery systems.
PubMed: 38746383
DOI: 10.1101/2024.05.01.592066 -
Ultrasonics Sonochemistry Jun 2024Chitosan nanoparticles (NPs) possess great potential in biomedical fields. Orifice-induced hydrodynamic cavitation (HC) has been used for the enhancement of fabrication...
Chitosan nanoparticles (NPs) possess great potential in biomedical fields. Orifice-induced hydrodynamic cavitation (HC) has been used for the enhancement of fabrication of size-controllable genipin-crosslinked chitosan (chitosan-genipin) NPs based on the emulsion cross-linking (ECLK). Experiments have been performed using various plate geometries, chitosan molecular weight and under different operational parameters such as inlet pressure (1-3.5 bar), outlet pressure (0-1.5 bar) and cross-linking temperature (40-70 °C). Orifice plate geometry was a crucial factor affecting the properties of NPs, and the optimized geometry of orifice plate was with single hole of 3.0 mm diameter. The size of NPs with polydispersity index of 0.359 was 312.6 nm at an optimized inlet pressure of 3.0 bar, and the maximum production yield reached 84.82 %. Chitosan with too high or too low initial molecular weight (e.g., chitosan oligosaccharide) was not applicable for producing ultra-fine and narrow-distributed NPs. There existed a non-linear monotonically-increasing relationship between cavitation number (C) and chitosan NP size. Scanning electron microscopy (SEM) test indicated that the prepared NPs were discrete with spherical shape. The study demonstrated the superiority of HC in reducing particle size and size distribution of NPs, and the energy efficiency of orifice type HC-processed ECLK was two orders of magnitude than that of ultrasonic horn or high shear homogenization-processed ECLK. In vitro drug-release studies showed that the fabricated NPs had great potential as a drug delivery system. The observations of this study can offer strong support for HC to enhance the fabrication of size-controllable chitosan-genipin NPs.
Topics: Chitosan; Nanoparticles; Iridoids; Hydrodynamics; Particle Size; Pressure; Temperature; Molecular Weight
PubMed: 38733852
DOI: 10.1016/j.ultsonch.2024.106899 -
Molecules (Basel, Switzerland) Apr 2024Bacterial infection is a thorny problem, and it is of great significance to developing green and efficient biological antibacterial agents that can replace antibiotics....
Bacterial infection is a thorny problem, and it is of great significance to developing green and efficient biological antibacterial agents that can replace antibiotics. This study aimed to rapidly prepare a new type of green antibacterial nanoemulsion containing silver nanoparticles in one step by using oil (BBO) as an oil phase and tea saponin (TS) as a natural emulsifier and reducing agent. The optimum preparation conditions of the AgNPs@BBO-TS NE were determined, as well as its physicochemical properties and antibacterial activity in vitro being investigated. The results showed that the average particle size of the AgNPs@BBO-TS NE was 249.47 ± 6.23 nm, the PDI was 0.239 ± 0.003, and the zeta potential was -35.82 ± 4.26 mV. The produced AgNPs@BBO-TS NE showed good stability after centrifugation and 30-day storage. Moreover, the AgNPs@BBO-TS NE had an excellent antimicrobial effect on , , and . These results demonstrated that the AgNPs@BBO-TS NE produced in this study can be used as an efficient and green antibacterial agent in the biomedical field.
Topics: Anti-Bacterial Agents; Silver; Metal Nanoparticles; Emulsions; Microbial Sensitivity Tests; Green Chemistry Technology; Particle Size; Staphylococcus aureus; Plant Oils; Pseudomonas aeruginosa; Escherichia coli; Saponins
PubMed: 38731501
DOI: 10.3390/molecules29092009 -
Molecules (Basel, Switzerland) Apr 2024In this study, we developed a green and multifunctional bioactive nanoemulsion (BBG-NEs) of oil using polysaccharide (BSP) and glycyrrhizic acid (GA) as natural...
In this study, we developed a green and multifunctional bioactive nanoemulsion (BBG-NEs) of oil using polysaccharide (BSP) and glycyrrhizic acid (GA) as natural emulsifiers. The process parameters were optimized using particle size, PDI, and zeta potential as evaluation parameters. The physicochemical properties, stability, transdermal properties, and bioactivities of the BBG-NEs under optimal operating conditions were investigated. Finally, network pharmacology and molecular docking were used to elucidate the potential molecular mechanism underlying its wound-healing properties. After parameter optimization, BBG-NEs exhibited excellent stability and demonstrated favorable in vitro transdermal properties. Furthermore, it displayed enhanced antioxidant and wound-healing effects. SD rats wound-healing experiments demonstrated improved scab formation and accelerated healing in the BBG-NE treatment relative to BBO and emulsifier groups. Pharmacological network analyses showed that AKT1, CXCL8, and EGFR may be key targets of BBG-NEs in wound repair. The results of a scratch assay and Western blotting assay also demonstrated that BBG-NEs could effectively promote cell migration and inhibit inflammatory responses. These results indicate the potential of the developed BBG-NEs for antioxidant and skin wound applications, expanding the utility of natural emulsifiers. Meanwhile, this study provided a preliminary explanation of the potential mechanism of BBG-NEs to promote wound healing through network pharmacology and molecular docking, which provided a basis for the mechanistic study of green multifunctional nanoemulsions.
Topics: Wound Healing; Animals; Emulsions; Emulsifying Agents; Rats; Antioxidants; Glycyrrhizic Acid; Molecular Docking Simulation; Polysaccharides; Green Chemistry Technology; Humans; Rats, Sprague-Dawley; Nanoparticles; Plant Oils; Fabaceae; Male; Particle Size; Cell Movement
PubMed: 38731484
DOI: 10.3390/molecules29091994 -
WMJ : Official Publication of the State... May 2024Tarka (trandolapril/verapamil hydrohloride extended-release) is a fixed-dose combination antihypertensive drug formed from verapamil hydrochloride and trandolapril....
INTRODUCTION
Tarka (trandolapril/verapamil hydrohloride extended-release) is a fixed-dose combination antihypertensive drug formed from verapamil hydrochloride and trandolapril. Toxicologic manifestations of Tarka overdose are altered mental status, bradycardia, hypotension, atrioventricular block (first-degree), hyperglycemia, metabolic acidosis, and shock.
CASE PRESENTATION
We report a case of Tarka toxicity in a 2-year-old girl who presented with altered mental status, cardiogenic shock, hypotension, bradycardia, severe metabolic acidosis, hyperglycemia, and first-degree atrioventricular block. We started fluid resuscitation, epinephrine, norepinephrine, and insulin. Because of the patient's hyperlactatemia and hypotension despite standard therapies, we initiated intravenous lipid emulsion (ILE) therapy, after which her condition improved promptly.
DISCUSSION
Tarka overdose may be life-threatening as it can cause cardiogenic shock. In our patient, the regression of lactate elevation in a short time with ILE therapy and the improvement of her general condition highlight the importance of ILE.
CONCLUSIONS
ILE is an alternative treatment method for acute lipophilic drug intoxications, such as Tarka.
Topics: Humans; Female; Fat Emulsions, Intravenous; Insulin; Drug Overdose; Verapamil; Child, Preschool; Drug Combinations; Antihypertensive Agents; Hypoglycemic Agents; Indoles
PubMed: 38718248
DOI: No ID Found -
Scientific Reports May 2024This research aims to investigate the potential of utilizing pomegranate peel powder (PPP) as a natural preservative in muffin preparation. Pomegranate peel is a rich... (Comparative Study)
Comparative Study
This research aims to investigate the potential of utilizing pomegranate peel powder (PPP) as a natural preservative in muffin preparation. Pomegranate peel is a rich source of bioactive compounds, including phenolics, flavonoids, and tannins, which possess high antioxidant and antimicrobial properties. The In-Vitro antifungal activity of pomegranate peel powder (8% PPP), potassium sorbate (0.1% PS) and calcium propionate (0.5% CP) was assessed against Penicillium sp. and Aspergillus sp. using poison food technique. The PPP showed the anti-fungal activity by delaying the growth of microorganism on media plate similar to the PS and CP. The effect of utilization of PPP on quality characteristics of muffins were compared with the muffins with chemical preservatives (0.1% PS and 0.5% CP). The viscosity and specific gravity of batter significantly increased from 7.98 to 11.87 Pa s and 1.089-1.398 respectively on addition of 8% PPP. The optical microscopic structure of PPP added batter revealed the decrease in the number of air cells from 24 to 12 with radius range of 6.42-72.72 μm and area range of 511.03-15,383.17 µm. The functional properties of flour with PPP had higher water absorption capacity, foaming stability, emulsification activity and emulsion stability than others. The addition of PPP significantly increase the weight (32.83 g), and decrease the height (31.3 mm), volume (61.43 cm), specific volume (1.67 cm/g) and baking loss (10.19%). The 418.36% increase in fibre content, 14.46% and 18.46% decrease in carbohydrates and energy value was observed in muffin with 8% PPP as compared to control respectively. The total phenols was increased from 0.92 to 12.5 mg GAE/100 g, total tannin from 0.2 to 8.27 mg GAE/100 g, In-vitro antioxidant activity by DPPH from 6.97 to 29.34% and In-vitro antioxidant activity by FRAP from 0.497 to 2.934 mg AAE/100 g in muffins added with 8% PPP. The muffin with PPP was softer than control and muffin with 0.1% PS. The addition of PPP resulted to improve in muffin texture but taste slightly bitter. During the storage of muffins at room temperature (27-30 °C), the moisture content of muffin with PPP was reduced from 17.04 to 13.23% which was higher than the rest of the treatments. Similarly, the hardness of sample with PPP was higher than the sample with 0.5% CP, but lowers than control and sample with 0.1% PS throughout the storage period. The results suggest that pomegranate peel powder can be successfully used as a natural preservative in place of chemical preservatives in muffins, to extend the shelf life. This study provides the opportunity to use PPP as functional ingredient and natural preservative in different bakery products.
Topics: Food Preservatives; Pomegranate; Powders; Food Preservation; Penicillium; Antioxidants; Antifungal Agents; Aspergillus; Fruit; Food Storage; Plant Extracts
PubMed: 38705878
DOI: 10.1038/s41598-024-61085-4