Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease with unknown cause. It mainly affects joints and, without proper treatment, negatively impacts their movement, causes painful deformities, and reduces the patients' quality of life. Current treatment options consist of various types of disease-modifying antirheumatic drugs (DMARDs), however 20-30% of patients are partially resistant to them. Therefore, development of new drugs is necessary. Possible option are compounds exhibiting their action via endocannabinoid system, which plays an important role in pain and inflammation modulation. One such compound - cannabidiol (CBD) has already been shown to attenuate synovitis in animal model of RA in in vivo studies. However, it has low bioavailability due to its low water solubility and lipophilicity. This issue can be addressed by preparation of a lipid containing formulation targeting lymphatic system, another route of absorption in the body. Materials and Methods: CBD-containing emulsion was prepared by high-shear homogenization and its droplet size distribution was analysed by optical microscopy. The relative oral bioavailability compared to oil solution as well as total availability of CBD were assessed in a cross-over study in rats and absorption of CBD via lymphatic system was observed. The effect of CBD on the animal model of RA was determined. Results: Compared to oil solution, the emulsion exhibited higher absolute oral bioavailability. Significant lymphatic transport of CBD was observed in all formulations and the concentrations in lymph were calculated. The therapeutic effect of CBD on RA was confirmed as an improvement in clinical symptoms as well as morphological signs of disease activity were observed during the study. Conclusion: In this work, we prepared a simple stable emulsion formulation, determined the pharmacokinetic parameters of CBD and calculated its absolute bioavailability in rats. Moreover, we successfully tested the pharmaceutical application of such a formulation and demonstrated the positive effect of CBD in an animal model of RA.
- MeSH
- aplikace orální MeSH
- bolest farmakoterapie MeSH
- emulze MeSH
- kanabidiol * farmakologie chemie MeSH
- klinické křížové studie MeSH
- krysa rodu rattus MeSH
- kvalita života MeSH
- revmatoidní artritida * farmakoterapie MeSH
- voda MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Sildenafil citrate has low oral bioavailability, systemic adverse effects, and a relatively delayed action. These issues may be addressed through direct transdermal delivery to the penis. This study aims to investigate the microemulsion formulation of the drug for effective transdermal delivery. Sildenafil citrate was formulated as a microemulsion using clove oil, dimethyl sulphoxide, phosphate buffer (pH 7), propylene glycol, Tween®80, and distilled water. Different proportions of these components were used to create six formulations of the microemulsion (F1-F6), which were then characterised by their physical appearance and clarity, pH, viscosity, conductivity, percent transmission, and droplet size. Furthermore, the stability, content analysis, in-vitro drug release, and transdermal permeation of sildenafil citrate from the generated drug-loaded microemulsions were studied. All prepared formulas contained nano-sized oil droplets (less than 20 nm), and the pH values were within the range of skin pH; however, two formulas were not transparent. Additionally, all formulations were thermodynamically stable, passing freeze-thaw, heating-cooling, and centrifugation tests. Next, the formulas demonstrated zero-order release kinetics, indicating that they can provide a sustained release profile for sildenafil citrate. Finally, the microemulsion formulation exhibited a 2.8-fold enhancement in skin permeation compared with that of the sildenafil citrate suspension. The prepared microemulsions demonstrated beneficial physical properties and skin permeation profiles that are promising for the local administration of sildenafil citrate.
- Klíčová slova
- mikroemulze,
- MeSH
- aplikace kožní * MeSH
- emulze MeSH
- hřebíčkový olej MeSH
- krysa rodu rattus MeSH
- lékové formy MeSH
- modely u zvířat MeSH
- permeabilita MeSH
- příprava léků metody MeSH
- sildenafil citrát * aplikace a dávkování farmakokinetika farmakologie MeSH
- stabilita léku MeSH
- suspenze MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- klinická studie MeSH
Druhá část cyklu o parenterální nutrici v neonatologii se zaměřuje na makronutrienty a energii. Makronutrienty poskytují primární nutriční zdroj energie a můžeme je rozdělit na bílkoviny (proteiny), tuky (lipidy) a cukry (sacharidy). V parenterální nutrici se bílkoviny dodávají ve formě aminokyselin, cukry ve formě glukózy a tuky jsou podávány v podobě intravenózních lipidových emulzí. Zhodnocení aktuálního stavu novorozence a biochemický monitoring přívodu makronutrientů jsou zásadní pro optimalizaci dodávky živin a prevenci závažných komplikací.
The second part of the neonatal parenteral nutrition series focuses on macronutrients and energy. Macronutrients provide the primary nutritional source of energy and can be classified into proteins, fats (lipids), and sugars (carbohydrates). In neonatal parenteral nutrition, proteins are provided in the form of amino acids, sugars in the form of glucose, and fats are administered in the form of intravenous lipid emulsions. Evaluating the condition of a newborn and biochemical monitoring of macronutrient intake are essential for optimizing nutrient delivery and preventing serious complications.
- MeSH
- aminokyseliny aplikace a dávkování klasifikace MeSH
- energetický příjem MeSH
- hypertriglyceridemie etiologie patologie MeSH
- krevní glukóza analýza MeSH
- lipidy fyziologie terapeutické užití MeSH
- novorozenec MeSH
- parenterální výživa * metody škodlivé účinky MeSH
- poruchy metabolismu glukózy etiologie MeSH
- proteiny terapeutické užití MeSH
- roztoky pro parenterální výživu analýza aplikace a dávkování farmakologie MeSH
- sacharidy terapeutické užití MeSH
- selhání střeva diagnóza etiologie farmakoterapie MeSH
- tukové emulze intravenózní aplikace a dávkování farmakologie klasifikace MeSH
- živiny * aplikace a dávkování klasifikace MeSH
- Check Tag
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
(1) Objectives: Intestinal failure in home parenteral nutrition patients (HPNPs) results in oxidative stress and liver damage. This study investigated how a high dose of fish oil (FO) added to various lipid emulsions influences antioxidant status and liver function markers in HPNPs. (2) Methods: Twelve HPNPs receiving Smoflipid for at least 3 months were given FO (Omegaven) for a further 4 weeks. Then, the patients were randomized to subsequently receive Lipoplus and ClinOleic for 6 weeks or vice versa plus 4 weeks of Omegaven after each cycle in a crossover design. Twelve age- and sex-matched healthy controls (HCs) were included. (3) Results: Superoxide dismutase (SOD1) activity and oxidized-low-density lipoprotein concentration were higher in all baseline HPN regimens compared to HCs. The Omegaven lowered SOD1 compared to baseline regimens and thus normalized it toward HCs. Lower paraoxonase 1 activity and fibroblast growth factor 19 (FGF19) concentration and, on the converse, higher alkaline phosphatase activity and cholesten concentration were observed in all baseline regimens compared to HCs. A close correlation was observed between FGF19 and SOD1 in baseline regimens. (4) Conclusions: An escalated dose of FO normalized SOD1 activity in HPNPs toward that of HCs. Bile acid metabolism was altered in HPNPs without signs of significant cholestasis and not affected by Omegaven.
Several studies have reported on application of cellulose particles for stabilizing Pickering emulsions (PE). Here we employ an original approach that involves using these particles as a part of advanced composite colloids made of conducting polymer polyaniline (PANI) and cellulose nanocrystals (CNC) or nanofibrils (CNF). PANI/cellulose particles were prepared using oxidative polymerization of aniline in situ in the presence of CNC or CNF. The type and amount of celluloses (CNC vs CNF) and concentration of precursors (aniline monomer and oxidant) used in the reaction determined properties of the colloidal particles, such as size, morphology and content of PANI. The particles demonstrated intriguing biological characteristics, including no cytotoxicity, antibacterial activity against Staphylococcus aureus and Escherichia coli, antioxidant activity and related immunomodulatory activity. For the first time, such composites were used to successfully stabilize oil-in-water PE with undecane or capric/caprylic triglyceride oils. The properties of the emulsions were determined by the PANI/cellulose particles and oil used. The key finding of the study is the demonstrated ability of PANI/cellulose particles to stabilize PE, as well as the excellent antioxidant activity and ROS scavenging action originating from PANI presence, indicating potential of such systems for use in biomedicine, particularly for wound healing.
Toxicity of β-blockers is one of the most common causes of poison-induced cardiogenic shock throughout the world. Therefore, methodologies for in vivo removal of the drugs from the body have been under investigation. Intralipid emulsion (ILE) is a common commercial lipid emulsion used for parenteral nutrition, but it has also been administered to patients suffering from drug toxicities. In this work, a set of β-blockers of different hydrophobicity's (log KD values ranging from 0.16 to 3.8) were investigated. The relative strength of the interactions between these compounds and the ILE was quantitatively assessed by means of binding constants and adsorption constants of the formed β-blocker-ILE complexes. The binding constants were determined by capillary electrokinetic chromatography and the adsorption constants were calculated based on different adsorption isotherms. Expectedly, the binding constants were strongly related to the log KD values of the β-blockers. The binding and adsorption constants also show that less hydrophobic β-blockers interact with ILE, suggesting that this emulsion could be useful for capturing such compounds in cases of their overdoses. Thus, the use of ILE for treatment of toxicities caused by a larger range of β-blockers is worth further investigation.
- MeSH
- beta blokátory MeSH
- chromatografie MeSH
- fosfolipidy * MeSH
- lidé MeSH
- sójový olej MeSH
- tukové emulze intravenózní * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Adhesions are the most common cause of long-term morbidity after abdominal surgery and most often cause various forms of intestinal passage disorders ranging from partial obstruction to complete, life-threatening intestinal obstruction. The aim of the present study was to evaluate the protective effect of intraperitoneally administered lipid emulsions on the formation of adhesions in larger animal model, as the lubricating effect of phospholipids and the mechanical barrier of the lipid component are combined with the anti-inflammatory effect of fish oil. METHODS: Thirty-one female domestic pigs were randomly divided into three groups. At the end of the surgical procedure, a lipid emulsion or saline solution was applied intraperitoneally. After 14 days, an independent macroscopic, histological and immunohistochemical evaluation of the adhesions were performed. RESULTS: Intraperitoneal administration of lipid emulsions significantly reduced the incidence of intra-abdominal adhesions. Microscopic examination demonstrated a significant reduction in the number of inflammatory elements and the amount of collagen in the adhesions, especially after administration of the fish oil-based emulsion. A simultaneous decrease in neovascularization was observed in the adhesions. Evaluation of the intestinal anastomosis did not reveal significant differences in healing between the groups. CONCLUSION: Intraperitoneal administration of lipid emulsions can reduce the development of postoperative intra-abdominal adhesions by the combined action of phospholipids as important lubricants and lipids as a mechanical barrier. Their effect is caused by a reduction in proinflammatory and profibrotic mediators. At the same time, intraperitoneal administration of lipid emulsions does not impair healing of the anastomosis in larger animal model.
- MeSH
- adheze tkání etiologie prevence a kontrola patologie MeSH
- anastomóza chirurgická metody MeSH
- emulze MeSH
- pooperační komplikace * prevence a kontrola patologie MeSH
- rybí oleje * terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie veterinární MeSH
- MeSH
- dospělí MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- pokus o sebevraždu MeSH
- tukové emulze intravenózní terapeutické užití MeSH
- venlafaxin hydrochlorid * otrava MeSH
- výsledek terapie MeSH
- zneužívání léků na předpis MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Branched copolymer surfactants (BCS) containing thermoresponsive polymer components, hydrophilic components, and hydrophobic termini allow the formation of emulsions which switch from liquid at room temperature to a gel state upon heating. These materials have great potential as in situ gel-forming dosage forms for administration to external and internal body sites, where the emulsion system also allows effective solubilisation of a range of drugs with different chemistries. These systems have been reported previously, however there are many challenges to translation into pharmaceutical excipients. To transition towards this application, this manuscript describes the evaluation of a range of pharmaceutically-relevant oils in the BCS system as well as evaluation of surfactants and polymeric/oligomeric additives to enhance stability. Key endpoints for this study are macroscopic stability of the emulsions and rheological response to temperature. The effect of an optimal additive (methylcellulose) on the nanoscale processes occurring in the BCS-stabilised emulsions is probed by small-angle neutron scattering (SANS) to better comprehend the system. Overall, the study reports an optimal BCS/methylcellulose system exhibiting sol-gel transition at a physiologically-relevant temperature without macroscopic evidence of instability as an in situ gelling dosage form.
PURPOSE: Osteoporosis is a severe health problem with social and economic impacts on society. The standard treatment consists of the systemic administration of drugs such as bisphosphonates, with alendronate (ALN) being one of the most common. Nevertheless, complications of systemic administration occur with this drug. Therefore, it is necessary to develop new strategies, such as local administration. METHODS: In this study, emulsion/dispersion scaffolds based on W/O emulsion of PCL and PF68 with ALN, containing hydroxyapatite (HA) nanoparticles as the dispersion phase were prepared using electrospinning. Scaffolds with different release kinetics were tested in vitro on the co-cultures of osteoblasts and osteoclast-like cells, isolated from adult osteoporotic and control rats. Cell viability, proliferation, ALP, TRAP and CA II activity were examined. A scaffold with a gradual release of ALN was tested in vivo in the bone defects of osteoporotic and control rats. RESULTS: The release kinetics were dependent on the scaffold composition and the used system of the poloxamers. The ALN was released from the scaffolds for more than 22 days. The behavior of cells cultured in vitro on scaffolds with different release kinetics was comparable. The difference was evident between cell co-cultures isolated from osteoporotic and control animals. The PCL/HA scaffold show slow degradation in vivo and residual scaffold limited new bone formation inside the defects. Nevertheless, the released ALN supported bone formation in the areas surrounding the residual scaffold. Interestingly, a positive effect of systemic administration of ALN was not proved. CONCLUSION: The prepared scaffolds enabled tunable control release of ALN. The effect of ALN was proved in vitro and in in vivo study supported peri-implant bone formation.
- MeSH
- alendronát * farmakologie MeSH
- emulze farmakologie MeSH
- hydroxyapatit farmakologie MeSH
- inhibitory kostní resorpce * farmakologie MeSH
- krysa rodu rattus MeSH
- osteoblasty MeSH
- osteogeneze MeSH
- osteoklasty MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
