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Clinical Toxicology (Philadelphia, Pa.) Jun 2022Lipid emulsion infusion is a first-line therapy against the toxicity of local anesthetics and is a potential treatment for other drug overdoses, especially for highly...
BACKGROUND
Lipid emulsion infusion is a first-line therapy against the toxicity of local anesthetics and is a potential treatment for other drug overdoses, especially for highly lipophilic drugs. Considering the lipophilic property of volatile anesthetics, we hypothesized that lipid emulsion could reverse general anesthesia.
METHODS
Using adult rats, we tested the effect of lipid emulsion infusion on time to emergence after discontinuation of sevoflurane and isoflurane, and further evaluated restoration of righting reflex under continuous sevoflurane anesthesia. Electroencephalogram during lipid emulsion infusion was also investigated under continuous sevoflurane inhalation. The effect of lipid emulsion on sevoflurane-induced respiratory and hemodynamic depressions was evaluated by measuring respiratory rate, PaCO (arterial partial pressure of CO), blood pressure, and heart rate. The binding property of lipid emulsion on sevoflurane and isoflurane was assessed using setting with a conical flask.
RESULTS
Lipid emulsion infusion significantly decreased time to emergence from sevoflurane anesthesia (131 ± 53 vs. 237 ± 69 s) and restored righting reflex during continuous sevoflurane inhalation, by comparing normal saline infusion. Consistent with the behavioral findings, the electroencephalogram under continuous sevoflurane showed decreased power of the bands at 5 min after the initiation of lipid emulsion infusion. In addition to reversing hypnosis, lipid emulsion recovered respiratory as well as hemodynamic depressions induced by sevoflurane. Decreased time to emergence was observed also in isoflurane anesthesia (203 ± 111 vs. 314 ± 154 s). To investigate the binding mechanism of lipid emulsion infusion, experiments revealed significantly decreased anesthetic concentrations of sevoflurane and isoflurane by mixing with lipid emulsion.
CONCLUSIONS
Lipid emulsion facilitated reversal from volatile anesthetics, as shown by several parameters. As lipid emulsion could bind to volatile anesthetics and simply decrease their effects, our findings suggest that lipid emulsion is a potentially useful agent to reverse general anesthesia.
Topics: Anesthetics, Inhalation; Animals; Emulsions; Humans; Isoflurane; Lipids; Methyl Ethers; Rats; Rodentia; Sevoflurane
PubMed: 34985393
DOI: 10.1080/15563650.2021.2020280 -
Journal of Agricultural and Food... Jul 2020The resistance in microorganisms against many conventional antibiotics has become a serious global health problem. However, antibacterial drug delivery materials are...
The resistance in microorganisms against many conventional antibiotics has become a serious global health problem. However, antibacterial drug delivery materials are still limited in toxicity, short efficacy and reducing inflammation. The novel and natural Pickering emulsions stabilized by antimicrobial peptide nanoparticles were tested as promising platforms to control bacterial resistance development. The parasin I interacted or conjugated with lecithin or chitosan and formed nanoparticles encapsulated by Pickering emulsion. The protonation and deprotonation of amino groups in chitosan and parasin I resulted in nanoparticles in different aggregate states and changed emulsion stability. Moreover, the Pickering emulsion could induce severe bacterial agglomeration on both Gram-positive and Gram-negative bacteria than parasin I through the membrane disintegration mechanism. Furthermore, the Pickering emulsion could alleviate the cytotoxicity of human liver cells and hemolytic activity in rat blood cells. In combination with the lack of acute cytotoxicity in Kunming mice and milder, more effective anti-inflammatory effect in peritonitis demonstrated for these Pickering emulsions, especially chitosan peptide-embedded nanoparticles Pickering emulsion, a potential role in combating multidrug resistant bacteria in biomedical applications.
Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Drug Carriers; Drug Compounding; Drug Delivery Systems; Emulsions; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Mice; Nanoparticles; Rats
PubMed: 32559384
DOI: 10.1021/acs.jafc.0c00874 -
AAPS PharmSciTech May 2022Nature has been used as therapeutic resources in the treatment of diseases for many years. However, some natural compounds have poor water solubility. Therefore,... (Review)
Review
Nature has been used as therapeutic resources in the treatment of diseases for many years. However, some natural compounds have poor water solubility. Therefore, physicochemical strategies and technologies are necessary for development of systems for carrying these substances. The self-emulsifying drug delivery systems (SEDDS) have been used as carriers of hydrophobic compounds in order to increase the solubility and absorption, improving their bioavailability. SEDDS are constituted with a mixture of oils and surfactants which, when come into contact with an aqueous medium under mild agitation, can form emulsions. In the last years, a wide variety of self-emulsifying formulations containing bioactive compounds from natural origin has been developed. This review provides a comprehensive overview of the main excipients and natural bioactive compounds composing SEDDS. In addition, applications, new technologies and innovation are reviewed as well. Examples of self-emulsifying formulations administered in different sites are also considered for a better understanding of the use of this strategy to modify the delivery of compounds from natural origin.
Topics: Administration, Oral; Biological Availability; Drug Delivery Systems; Emulsions; Excipients; Solubility
PubMed: 35534702
DOI: 10.1208/s12249-022-02291-z -
Advances in Colloid and Interface... Oct 2022In the early 20th century, Pickering and Ramsden revealed that solid particles could be utilized as emulsion stabilizers. Later, it was shown that particles can be used... (Review)
Review
In the early 20th century, Pickering and Ramsden revealed that solid particles could be utilized as emulsion stabilizers. Later, it was shown that particles can be used to aid in stablilization of foam as well. Differentiated from the emulsions/foams constructed by using surfactant agents, particle-stabilization offers significant advantages, such as better interfacial stability, non-toxicity, and less sensitive to environmental influences. Therefore, particle-stabilized foam and emulsion systems have the potential to gain more applications in the food, drug delivery, and cosmetic field. The internal mechanism and principle of particle stabilization interface have been clarified by introducing the classic mechanism of Pickering stabilization. By summarizing the additional/different effects of the protein, the relationship between the adaptive behavior of the protein in the interface and the protein structure has been explained. Furthermore, the functions of protein besides interface stabilization are introduced, such as encapsulation, taste masking and the catalytic properties of Pickering particles. Finally, deep thinking was triggered based on the existing research foundation, a new concept of "edible capillary foam" was proposed, and a new outlook was made. It is anticipated that the perception acquired from the current intense activity in this field will help researchers to reform existing materials and invent additional formulations, facilitating the exploration of additional engineering applications.
Topics: Emulsions; Food; Proteins; Surface-Active Agents
PubMed: 36054943
DOI: 10.1016/j.cis.2022.102743 -
Drug Delivery and Translational Research Jan 2022The purpose of this study was to develop and evaluate nanoemulsions (NEs) containing besifloxacin for ocular drug delivery. Pseudo ternary phase diagrams were...
The purpose of this study was to develop and evaluate nanoemulsions (NEs) containing besifloxacin for ocular drug delivery. Pseudo ternary phase diagrams were constructed using Triacetin (oil), Cremophor RH 40 (surfactant), and TranscutolP (co-surfactant) to identify NE regions. Six formulations were developed by low-energy emulsification method and then evaluated for size, refractive index, pH, osmolality, viscosity, and drug release. After accelerated physical stability and bovine conrneal permeation studies, NE2 was chosen as optimized formulation forantimicrobial efficacy, and hen's egg test-chorioallantoic membrane (HET-CAM) tests. The particle size of optimum NE was 14 nm with a narrow size distribution. Moreover, other physicochemical characterizations were in the acceptable range for ocular administration. Besifloxacin-loaded NEs demonstrated sustained release pattern and 1.7-fold higher permeation compared with the control suspension in the ex vivo transcorneal permeation study. HET-CAM test indicated no irritation, and HL% revealed no damage to the tissue, so the optimum NE is well tolerated by the eye. In vitro antimicrobial evaluation, showed comparative efficacy of lower drug-loaded NE (0.2%) versus 0.6% besifloxacin suspension (equal concentration to commercial besifloxacin eye drop). In conclusion, besifloxacin-loaded NEs could be considered as a suitable alternative to the marketed suspension for treating bacterial eyeinfections.
Topics: Administration, Ophthalmic; Animals; Azepines; Cattle; Chickens; Emulsions; Female; Fluoroquinolones
PubMed: 33575973
DOI: 10.1007/s13346-021-00902-z -
Journal of Controlled Release :... Nov 2020The purpose of this study is to investigate the process of drug distribution and mechanism of drug release of ophthalmic emulsions in the context of factors associated...
The purpose of this study is to investigate the process of drug distribution and mechanism of drug release of ophthalmic emulsions in the context of factors associated with the drug release. Cyclosporine and difluprednate emulsions were chosen as model systems. A kinetic method was used to quantitatively evaluate the drug distribution within a simplified biphasic (emulsion) system. The impacts of release associated factors were investigated, including the amount of sodium dodecyl sulfate (SDS), ethanol, and ionic strength in the release medium as well as the temperature. SDS and ethanol were found to significantly enhance both rate and extent of drug diffusion from oil to aqueous phase for both cyclosporine and difluprednate emulsions. The ionic strength was found to decrease the rate and extent of cyclosporine transfer from oil to aqueous phase but had little impact on the transfer of difluprednate between phases. Diffusion of cyclosporine to aqueous phase exhibited a decreasing trend with increasing temperature due to its atypical temperature dependent solubility in water. Based on our previous method to investigate the impact of formulation variables on drug diffusion and the findings in the current study, a biphasic release model for emulsions is proposed and discussed. Lastly, the underlying relationship of three key quality attributes (i.e., globule size distribution, drug distribution, and release characteristics) and their effect on product quality and performance were discussed. This study provides a fundamental insight into the drug distribution and release in complex emulsion systems. It also elucidates the critical variables for the development of in vitro release method to support regulatory assessment of ophthalmic emulsions and formulation development.
Topics: Cyclosporine; Diffusion; Drug Liberation; Emulsions; Solubility; Water
PubMed: 32822741
DOI: 10.1016/j.jconrel.2020.08.020 -
Annals of Palliative Medicine Dec 2021The purpose of this study was to evaluate the effects of monovalent and divalent cations on the stability of a fat emulsion (Lipovenoes MCT) in total nutrient admixtures...
BACKGROUND
The purpose of this study was to evaluate the effects of monovalent and divalent cations on the stability of a fat emulsion (Lipovenoes MCT) in total nutrient admixtures (TNAs) by testing the percentage of fat residing in globules >5 µm (PFAT5) values.
METHODS
TNAs with different combinations of glucose (5% and 10%), amino acids (3.35 and 4.5 g/100 mL), Na+/K+ (100/39 mmol/L), Mg2+ (3.4 and 2.7 mmol/L), and fat emulsion (2.4%) were tested in triplicate at room temperature. The pH, mean droplet size (MDS), and PFAT5 were assessed at 0, 6, 12, 24, 36, and 48 h.
RESULTS
In all seven groups, the TNA globule distribution was uniform, the pH value fluctuated in the range of 5.93-6.06, and the MDS met the limit of the United States Pharmacopeia (USP) within 48 h. The PFAT5 value of the control group 0 without electrolytes was the lowest; group 1 added monovalent ions of 139 mmol/L was significantly higher (P<0.05) but without exceed the USP limit after 48 h. Groups 2 and 3 added Mg2+ 3.4 and 2.7 mmol/L respectively, based on group 1. Group 4 increased the amino acid concentration from 3.35% to 4.5% based on group 2, and group 5 reduced the glucose concentration from 10% to 5% based on group 4. Group 6 removed monovalent ions and retained only Mg2+ based on group 5. The PFAT5 values of group 2, 3, 4, and 5 exceeded the limit after 6 h and group 6 after 12 h. There was no statistical difference between group 2 and 4 (P>0.05) or between group 4 and 5 (P>0.05).
CONCLUSIONS
When the concentration of glucose is 10-25% and the amino acid is 2.5-4.5%, The addition of monovalent ions affects the stability of fat emulsion in TNAs, however when the concentrations of Na+ ≤100 mmol/L and K+ ≤39 mmol/L, the PFAT5 value will not exceed the USP limit within 24 h. Mg2+ has a significant effect, the PFAT5 value will exceed the USP limit after 6 h when the concentration ≥2.7 mmol/L, which may cause potential safety hazards.
Topics: Drug Stability; Fat Emulsions, Intravenous; Glucose; Humans; Nutrients; Particle Size
PubMed: 35016476
DOI: 10.21037/apm-21-3353 -
Lipid emulsion attenuates extrinsic apoptosis induced by amlodipine toxicity in rat cardiomyoblasts.Human & Experimental Toxicology Apr 2021Amlodipine-induced toxicity has detrimental effects on cardiac cells. The aim of this study was to examine the effect of lipid emulsion on decreased H9c2 rat...
Amlodipine-induced toxicity has detrimental effects on cardiac cells. The aim of this study was to examine the effect of lipid emulsion on decreased H9c2 rat cardiomyoblast viability induced by amlodipine toxicity. The effects of amlodipine, lipid emulsion, LY 294002, and glibenclamide, either alone or in combination, on cell viability and count, apoptosis, and expression of cleaved caspase-3 and -8, and Bax were examined. LY 294002 and glibenclamide partially reversed lipid emulsion-mediated attenuation of decreased cell viability and count induced by amlodipine. Amlodipine increased caspase-3 and -8 expression, but it did not alter Bax expression. LY 294002 and glibenclamide reversed lipid emulsion-mediated inhibition of cleaved caspase-3 and -8 expression induced by amlodipine. Lipid emulsion inhibited early and late apoptosis induced by amlodipine. LY 294002 and glibenclamide inhibited lipid emulsion-mediated inhibition of late apoptosis induced by amlodipine, but they did not significantly alter lipid emulsion-mediated inhibition of early apoptosis induced by amlodipine. Lipid emulsion decreased amlodipine-induced TUNEL-positive cells. These results suggest that lipid emulsion inhibits late apoptosis induced by amlodipine at toxic dose via the activation of phosphoinositide-3 kinase and ATP-sensitive potassium channels in the extrinsic apoptotic pathway.
Topics: Amlodipine; Animals; Antihypertensive Agents; Apoptosis; Cell Line; Cell Survival; Emulsions; Myoblasts, Cardiac; Phospholipids; Rats; Soybean Oil
PubMed: 33030052
DOI: 10.1177/0960327120964551 -
Reproductive Sciences (Thousand Oaks,... Feb 2022A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel...
A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug.
Topics: 2-Propanol; Acetamides; Acetates; Acetone; Acetonitriles; Animals; Emulsions; Ethanol; Female; Mice; Myometrium; Solvents; Tocolytic Agents; Uterine Contraction
PubMed: 33852137
DOI: 10.1007/s43032-021-00576-5 -
ACS Macro Letters Aug 2022Crystalsomes are crystalline capsules that are formed by controlling polymer crystallization to break translational symmetry. While recent studies showed that these...
Crystalsomes are crystalline capsules that are formed by controlling polymer crystallization to break translational symmetry. While recent studies showed that these crystalline capsules exhibit interesting mechanical properties, thermal behavior, and excellent performance in blood circulation, the closed capsule is undesired for drug delivery applications. We report the formation and characterization of porous crystalsomes where porosity is rendered on the crystalline shells. A miniemulsion is formed using two amphiphilic block copolymers (BCP). The competition between controlled crystallization and phase separation of the BCPs at the emulsion surface leads to multiphase crystalsomes. Subsequently removing one BCP produces porous crystalline capsules.
Topics: Capsules; Crystallization; Emulsions; Polymers; Porosity
PubMed: 35901196
DOI: 10.1021/acsmacrolett.2c00347