Léčivé přípravky pro intravenózní podání často obsahují kromě farmakologicky účinné látky i pomocné látky, které zajišťují rozpustnost, stabilitu a správné pH léčiva. Tradičně se předpokládá, že pomocné látky jsou biologicky inertní, avšak tento předpoklad není vždy naplněn. Některé pomocné látky mohou způsobovat hypersenzitivní reakce, indukovanou orgánovou toxicitu, diskomfort při aplikaci či vykazovat vlastní biologické účinky. Regulace těchto látek se liší podle jejich známých účinků, a tak ne vždy je kvantitativ- ní obsah těchto látek specifikován. Tento článek se zaměřuje na tři často používané pomocné látky v intravenózních lékových formách – propylenglykol, polysorbát 80 a sulfobutylether-β-cyklodextrin (SBECD). V článku analyzujeme farmakologické profily těchto látek, jejich potenciální toxicitu a možnosti prevence nežádoucích účinků, s důrazem na jejich použití u kriticky nemocných dospělých pacientů, kde intravenózní podání léků je často jedinou možností. Tento přístup je zásadní pro minimalizaci rizik spojených s použitím těchto pomocných látek v intenzivní medicíně.
Medicinal products for intravenous administration often contain excipients, in addition to the pharmacologically active substance, that ensure the solubility, stability and correct pH of the drug. Excipients are assumed to be biologically inert, but this assumption is not always met. Some excipients may cause hypersensitivity reactions, organ toxicity, discomfort on administration or show own biological effects The regulatory framework for these substances varies according to their known effects, thus the quantitative content of these substances is not always compulsory to be specified. This article focuses on three frequently used excipients in intravenous drug dosage forms - propylene glycol, polysorbate 80 and sulfobutyl ether-β-cyclodextrin (SBECD). In this article, we discuss the pharmacological profiles of these agents, their potential toxicity, and options for preventing adverse effects, with an emphasis on their use in critically ill adults where intravenous drug administration is often the only option. This approach is essential to minimise the risks associated with the use of these excipients in critically ill.
- Keywords
- sulfobutylether-β-cyklodextrin,
- MeSH
- Administration, Intravenous methods MeSH
- Humans MeSH
- Drug-Related Side Effects and Adverse Reactions * drug therapy classification MeSH
- Polysorbates pharmacology classification metabolism MeSH
- Excipients * pharmacology adverse effects MeSH
- Propylene Glycol pharmacology metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® ChiraldexTM G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a LipodexTM D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-β-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the ChiraldexTM G-PN column. Six baseline and nine partial separations were observed with the LipodexTM D column, respectively.
The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions.
- MeSH
- Analgesics pharmacology therapeutic use MeSH
- beta-Cyclodextrins * pharmacology MeSH
- Pain chemically induced drug therapy metabolism MeSH
- CHO Cells MeSH
- Cholesterol metabolism MeSH
- Cricetulus MeSH
- HEK293 Cells MeSH
- TRPM Cation Channels * metabolism genetics MeSH
- Humans MeSH
- Membrane Microdomains metabolism drug effects MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Pregnenolone pharmacology MeSH
- Pyrimidinones pharmacology MeSH
- Sphingomyelin Phosphodiesterase * metabolism pharmacology MeSH
- Cell Survival drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Non-alcoholic fatty liver disease (NAFLD) is a general term for fatty liver disease not caused by viruses or alcohol. Fibrotic hepatitis, cirrhosis, and hepatocellular carcinoma can develop. The recent increase in NAFLD incidence worldwide has stimulated drug development efforts. However, there is still no approved treatment. This may be due in part to the fact that non-alcoholic steatohepatitis (NASH) pathogenesis is very complex, and its mechanisms are not well understood. Studies with animals are very important for understanding the pathogenesis. Due to the close association between the establishment of human NASH pathology and metabolic syndrome, several animal models have been reported, especially in the context of overnutrition. In this study, we investigated the induction of NASH-like pathology by enhancing cholesterol absorption through treatment with hydroxypropyl-beta-cyclodextrin (CDX). Female Sprague-Dawley rats were fed a normal diet with normal water (control group); a high-fat (60 kcal%), cholesterol (1.25 %), and cholic acid (0.5 %) diet with normal water (HFCC group); or HFCC diet with 2 % CDX water (HFCC+CDX group) for 16 weeks. Compared to the control group, the HFCC and HFCC+CDX groups showed increased blood levels of total cholesterol, aspartate aminotransferase, and alanine aminotransferase. At autopsy, parameters related to hepatic lipid synthesis, oxidative stress, inflammation, and fibrosis were elevated, suggesting the development of NAFLD/NASH. Elevated levels of endoplasmic reticulum stress-related genes were evident in the HFCC+CDX group. In the novel rat model, excessive cholesterol intake and accelerated absorption contributed to NAFLD/NASH pathogenesis.
- MeSH
- Cholesterol MeSH
- Diet, High-Fat adverse effects MeSH
- 2-Hydroxypropyl-beta-cyclodextrin metabolism therapeutic use MeSH
- Hypercholesterolemia * metabolism MeSH
- Hyperlipidemias * MeSH
- Liver metabolism MeSH
- Rats MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Non-alcoholic Fatty Liver Disease * chemically induced MeSH
- Rats, Sprague-Dawley MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
CONTEXT: Chlordecone (CLD) and β-hexachlorocyclohexane (β-HCH) are chlorinated pesticides that coexist as persistent organic pollutants in the groundwater of several countries in the Caribbean, being an environmental issue. This work evaluates theoretically the competitive formation of host-guest complexes pesticides@cyclodextrines (CDs) as an alternative for water purification and selective separation of pesticides. METHODS: Quantum mechanical calculations based on density functional theory (DFT) and classical molecular dynamics (MD) simulations were used to achieve information on geometries, energies, structure, and dynamics of guest-host complexes in the gas phase, implicit solvent medium, and in aqueous solutions. RESULTS: DFT studies showed that interactions of both pesticides with CDs are mediated by steric factors and guided by maximization of the hydrophobic interactions either with the other pesticide or with the CD cavity's inner atoms. MD results corroborate the formation of stable complexes of both pesticides with the studied CDs. α-CD exhibited a preference for the smaller β-HCH molecule over the CLD that could not perturb the formed complex. CONCLUSIONS: The simulation of competitive formation with γ-CD illustrated that this molecule could accommodate both pesticides inside its cavity. These results suggest that CDs with smaller cavity sizes such as α-CD could be used for selective separation of β-HCH from CLD in water bodies, while γ-CD could be used for methods that aim to remove both pesticides at the same time.
- Publication type
- Journal Article MeSH
Svalová relaxancia jsou nejčastějšími léčivy způsobujícími alergické reakce v perioperačním období. Vzhledem k intravenóznímu podání léčiv během celkové anestezie mohou být tyto reakce potenciálně život ohrožující. V kazuistice popisujeme případ rokuroniem indukovaného anafylaktického šoku u 26leté ženy s podezřením na mimoděložní těhotenství úspěšně léčeného podáním sugammadexu.
Muscle relaxants are the most common cause of allergic reactions during the perioperative period. This reaction could be potentially life-threatening because of the intravenous route of administration of the drugs used for general anesthesia. We describe a case of rocuronium-induced anaphylactic shock in a 26-years-old woman with suspected extrauterine pregnancy successfully treated with sugammadex.
- MeSH
- Anaphylaxis * etiology drug therapy MeSH
- Adult MeSH
- Humans MeSH
- Pregnancy, Ectopic surgery MeSH
- Rocuronium * adverse effects MeSH
- Sugammadex administration & dosage therapeutic use MeSH
- Pregnancy MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Svalová relaxancia se používají při téměř dvou třetinách anestezií. V případě jejich použití je důležitá následná důsledná reverze nervosvalové blokády, neboť pooperační reziduální kurarizace zvyšuje pooperační morbiditu. K reverzi svalové blokády lze využít sugammadex, který se vyznačuje velmi dobrou účinností a výhodným bezpečnostním profilem; největší přínos z jeho použití byl dokumentován u nemocných ve věku > 65 let, se skóre ASA ≥ III či s indexem tělesné hmotnosti > 35 a u pacientů podstupujících laparoskopický výkon. Podání sugammadexu brání vzniku pooperačních komplikací, zvyšuje bezpečnost pro pacienta a v současné době lze sugammadex považovat za standard, jehož využití by mělo být zvažováno u výrazně většího spektra pacientů, než tomu bylo dosud.
Muscle relaxants are used in almost two-thirds of anaesthesias. In case they are used, subsequent adequate reversal of neuromuscular blockade is crucial, as post- operative residual curarisation increases postoperative morbidity. For neuromuscular blockade reversal sugammadex can be used which has a very good efficacy and favourable safety profile; the greatest benefit from its use has been shown in patients aged > 65 years, with ASA score ≥ III or body mass index > 35, and in patients undergoing laparoscopic surgery. The administration of sugammadex prevents the development of postoperative complications and increases safety of the patients. Currently, sugammadex can be considered as a standard of care and should be offered to a much wider range of patients than has been the case to date.
Nanosponges with three-dimensional (3D) porous structures, narrow size distribution, and high entrapment efficiency are widely engineered for cancer therapy and drug delivery purposes. They protect the molecular agents from degradation and help to improve the solubility of lipophilic therapeutic agents/drugs with targeted delivery options in addition to being magnetized to attain suitable magnetic features. Nanosponge-based delivery systems have been applied for cancer therapy with high specificity, biocompatibility, degradability, and prolonged release behavior. In this context, the drug loading within nanosponges is influenced by the crystallization degree. Notably, 3D printing technologies can be applied for the development of novel nanosponge-based systems for biomedical applications. The impacts of polymers, cross-linkers, type of drugs, temperature, loading and mechanism of drug release, fabrication methods, and substitution degree ought to be analytically evaluated. Eco-friendly techniques for the manufacturing of nanosponges still need to be uncovered in addition to the existing methods, such as solvent techniques, ultrasound-assisted preparation, melting strategies, and emulsion solvent diffusion methods. Herein, the recent advancements associated with the drug delivery and cancer therapy potential of nanosponges (chiefly, cyclodextrin-based, DNAzyme, and ethylcellulose nanosponges) are deliberated, focusing on the important challenges and future perspectives.
- Publication type
- Journal Article MeSH
- Review MeSH
Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, β, and δ-damascone and inclusion complexes with β-cyclodextrin against different Candida spp. The inclusion complex of β-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (βDA-βCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC50 and cell viability curve constructions were performed using the microdilution method. The minimum fungicidal concentration (MFC) was determined by the subculture method in a solid medium. The α, β, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. β-damascone showed effective complexation in the three molar proportions assayed; however, none of the inclusion complexes was demonstrated clinically significant effects against the fungal tested. Then, all compounds have shown promising antifungal activities; however, in vivo assays are necessary to have therapeutical application in the future.
In this study, a sensitive platform was designed for the electrocatalytical oxidation and recognition of ascorbic acid (AA) based on poly(β-cyclodextrin) modified glassy carbon electrode (p(β-CD-GCE). Electropolymerization of β-CD on the surface of GCE was performed on the potential range of -1 to 1.5 V. So, a novel biopolymer was prepared on the surface of GCE towards sensitive recognition of AA in human plasma samples. The developed platform has good sensitivity and accuracy for electrooxidation and detection of AA with lower limit of quantification (LLOQ) of 1 nM and linear range of 1 nM to 100 mM. Moreover, the designed electrochemical sensor was employed for the analysis of AA on human plasma samples with high sensitivity. Based on advantages of p(β-CD) prepared by electropolymerization procedure (green, fast, homogeny, and efficient eletrocatalytical behaviour), this conductive biopolymer showed excellent analytical behaviour towards electrooxidation of AA. It is expected that the prepared polymeric interface is able to use in the analysis of biological species in clinical samples.
- MeSH
- beta-Cyclodextrins MeSH
- Biocompatible Materials MeSH
- Biopolymers MeSH
- Electrochemical Techniques * methods MeSH
- Ascorbic Acid * MeSH
- Humans MeSH
- Propylene Glycols MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
