Treating oral diseases remains challenging as API is quickly washed out of the application site by saliva turnover and mouth movements. In situ gels are a class of application forms that present sol-gel transition's ability as a response to stimuli. Their tunable properties are provided using smart polymers responsible for stimuli sensitivity, often providing mucoadhesivity. In this study, antimicrobial in situ gels of thermosensitive and pH-sensitive polymers loaded with silver nanoparticles were prepared and evaluated. The nanoparticles were prepared by green synthesis using Agrimonia eupatoria L. extract. According to the data analysis, the in situ gel with the most promising profile contained 15 % of Pluronic® F-127, 0.25 % of methylcellulose, and 0.1 % of Noveon® AA-1. Pluronic® F-127 and methylcellulose significantly increased the viscosity of in situ gels at 37 °C and shear rates similar to speaking and swallowing. At 20 °C, a behavior close to a Newtonian fluid was observed while being easily injectable (injection force 13.455 ± 1.973 N). The viscosity of the formulation increased with temperature and reached 2962.77 ± 63.37 mPa·s (37 °C). A temperature increase led to increased adhesiveness and rigidity of the formulation. The critical sol-gel transition temperature at physiological pH was 32.65 ± 0.35 °C. 96.77 ± 3.26 % of Ag NPs were released by erosion and dissolution of the gel after 40 min. The determination of MIC showed effect against E. coli and S. aureus (0.0625 mM and 0.5000 mM, respectively). The relative inhibition zone diameter of the in situ gel was 73.32 ± 11.06 % compared to gentamicin sulfate. This work discusses the optimization of the formulation of novel antibacterial in situ gel for oromucosal delivery, analyses the impact of the concentration of excipients on the dependent variables, and suggests appropriate evaluation of the formulation in terms of its indication. This study offers a promising dosage form for local treatment of oral diseases.
Pharmaceutical nanocrystals represent a promising new formulation that combines the benefits of bulk crystalline materials and colloidal nanoparticles. To be applied in vivo, nanocrystals must meet several criteria, namely colloidal stability in physiological media, non-toxicity to healthy cells, avoidance of macrophage clearance, and bioactivity in the target tissue. In the present work, curcumin, a naturally occurring poorly water-soluble molecule with a broad spectrum of bioactivity has been considered a candidate substance for preparing pharmaceutical nanocrystals. Curcumin nanocrystals in the size range of 40-90 nm were prepared by wet milling using the following combination of steric and ionic stabilizers: Tween 80, sodium dodecyl sulfate, Poloxamer 188, hydroxypropyl methylcellulose, phospholipids (with and without polyethylene glycol), and their combination. Nanocrystals stabilized by a combination of phospholipids enriched with polyethylene glycol proved to be the most successful in all evaluated criteria; they were colloidally stable in all media, exhibited low macrophage clearance, and proved non-toxic to healthy cells. This curcumin nanoformulation also exhibited outstanding anticancer potential comparable to commercially used cytostatics (IC50 = 73 μM; 24 h, HT-29 colorectal carcinoma cell line) which represents an improvement of several orders of magnitude when compared to previously studied curcumin formulations. This work shows that the preparation of phospholipid-stabilized nanocrystals allows for the conversion of poorly soluble compounds into a highly effective "solution-like" drug delivery system at pharmaceutically relevant drug concentrations.
- MeSH
- deriváty hypromelózy MeSH
- dodecylsíran sodný chemie MeSH
- fosfolipidy MeSH
- kurkumin * chemie farmakologie MeSH
- léčivé přípravky MeSH
- makrofágy MeSH
- nanočástice * chemie MeSH
- poloxamer chemie MeSH
- polyethylenglykoly chemie MeSH
- polysorbáty MeSH
- rozpustnost MeSH
- velikost částic MeSH
- voda MeSH
- Publikační typ
- časopisecké články MeSH
The use of biocompatible hydrogels has widely extended the potential of additive manufacturing (AM) in the biomedical field leading to the production of 3D tissue and organ analogs for in vitro and in vivo studies.In this work, the direct-write deposition of thermosensitive hydrogels is described as a facile route to obtain 3D cell-laden constructs with controlled 3D structure and stable behavior under physiological conditions.
- MeSH
- 3D tisk * MeSH
- algináty chemie MeSH
- hydrogely chemie MeSH
- lidé MeSH
- mikrotechnologie metody MeSH
- poloxamer chemie MeSH
- polymery chemická syntéza chemie MeSH
- tkáňové inženýrství přístrojové vybavení MeSH
- tkáňové podpůrné struktury chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops-tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear-air interface.
- MeSH
- film jako téma * MeSH
- fluorescenční mikroskopie metody MeSH
- kvartérní amoniové sloučeniny chemie MeSH
- lidé MeSH
- lipidy chemie MeSH
- mastné alkoholy chemie MeSH
- meibomské žlázky metabolismus MeSH
- poloxamer chemie MeSH
- simulace molekulární dynamiky * MeSH
- teoretické modely MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In the present work, we developed a novel needleless emulsion electrospinning technique that improves the production rate of the core/shell production process. The nanofibres are based on poly-ε-caprolactone (PCL) as a continuous phase combined with a droplet phase based on Pluronic F-68 (PF-68). The PCL-PF-68 nanofibres show a time-regulated release of active molecules. Needleless emulsion electrospinning was used to encapsulate a diverse set of compounds to the core phase [i.e. 5-(4,6-dichlorotriazinyl) aminofluorescein -PF-68, horseradish peroxidase, Tetramethylrhodamine-dextran, insulin growth factor-I, transforming growth factor-β and basic fibroblast growth factor]. In addition, the PF-68 facilitates the preservation of the bioactivity of delivered proteins. The system's potential was highlighted by an improvement in the metabolic activity and proliferation of mesenchymal stem cells. The developed system has the potential to deliver susceptible molecules in tissue-engineering applications.
- MeSH
- biokompatibilní materiály farmakologie MeSH
- dextrany chemie MeSH
- emulze chemie MeSH
- jehly MeSH
- kolagen typ II metabolismus MeSH
- křenová peroxidasa metabolismus MeSH
- mezenchymální kmenové buňky cytologie účinky léků metabolismus MeSH
- mezibuněčné signální peptidy a proteiny farmakologie MeSH
- miniaturní prasata MeSH
- nanovlákna chemie ultrastruktura MeSH
- poloxamer chemie MeSH
- polyestery chemie MeSH
- prasata MeSH
- proteiny aplikace a dávkování MeSH
- rhodaminy chemie MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury chemie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Práce studuje lisovatelnost a dobu rozpadu tablet ze směsného suchého pojiva DisintequikTM MCC v kombinaci se dvěma mazadly ve dvou koncentracích v závislosti na lisovací síle. Dále porovnává stejné parametry u fyzikálních směsí sprejově sušené laktosy Flowlacu? 100 a mikrokrystalické celulosy Microcelu? MC-102 v poměrech 1 : 9, 2 : 8 a 3 : 7 opět v kombinaci se dvěma mazadly ve dvou koncentracích při jedné lisovací síle. Použitá mazadla jsou stearan hořečnatý a poloxamer 407 v koncentraci 1% a 2%. Lisovatelnost je hodnocena pomocí energetické bilance lisování a pevnosti tablet v tahu. DisintequikTM MCC vykazuje vyšší hodnoty celkové energie lisování díky vyšším hodnotám energie akumulované tabletou, vyšší plasticitu, vyšší pevnost a delší dobu rozpadu tablet než obsahově odpovídající fyzikální směs sprejově sušené laktosy a mikrokrystalické celulosy.
The paper studies the compressibility and disintegration time of tablets from the co-processed dry binder DisintequikTM MCC in combination with two lubricants at two concentrations in dependence on compression force. It also compares identical parameters in the physical mixtures of the spray-dried lactose Flowlac? 100 and the microcrystalline cellulose Microcel? MC-102 in the ratios of 9 : 1, 8 : 2 and 7 : 3, again in combination with two lubricants of two concentrations at one compression force. The lubricants employed are magnesium stearate and poloxamer 407 in concentrations of 1% and 2%. Compressibility is evaluated by means of energy balance of compression and tensile strength of tablets. DisintequikTM MCC shows higher values of total energy of compression due to higher values of the energy accumulated by the tablet, higher plasticity, higher strength and a longer disintegration time of tablets than the physical mixture of spray-dried lactose and microcrystalline cellulose of a corresponding content.
- MeSH
- celulosa MeSH
- chemie fyzikální metody MeSH
- farmaceutická technologie MeSH
- farmaceutické pomocné látky MeSH
- lidé MeSH
- pevnost v tahu MeSH
- pevnost v tlaku MeSH
- poloxamer MeSH
- pomocné látky MeSH
- příprava léků MeSH
- rozpustnost MeSH
- stearany MeSH
- tablety MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The study evaluates the micronized poloxamers Lptrol micro127 (poloxamer 407) and Lptrol micro 68 (poloxamer 188) as lubricants in combination with the dry binders microcrystalline cellulose and spray-dried lactose. Magnesium stearate was employed as the comparative lubricant. The parameters under study included energy for friction, plasticity, ejection force, tensile strength of tablets, and disintegration time of tablets. The factors of influence were the concentration of lubricants, compression force, and mixing parameters. The lubricating effect of micronized poloxamers was smaller than that of magnesium stearate. Higher concentrations of poloxamers decreased the tensile strength of tablets from microcrystalline cellulose, shortened the disintegration time, and slightly prolonged the disintegration time in the case of spray-dried lactose. Parameters of mixing of dry binders with poloxamers influenced the tested parameters of compression more in the case of spray-dried lactose. In microcrystalline cellulose, they influenced more the tensile strength and disintegration time of tablets.
- MeSH
- časové faktory MeSH
- celulosa chemie MeSH
- chemie farmaceutická MeSH
- farmaceutická technologie metody MeSH
- kyseliny stearové chemie MeSH
- laktosa chemie MeSH
- lubrikanty chemie MeSH
- pevnost v tahu MeSH
- poloxamer chemie MeSH
- pomocné látky chemie MeSH
- rozpustnost MeSH
- tablety MeSH
- tření MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
We synthesized statistical poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazolines) (POXs) that are molecularly dissolved below their cloud point temperature in aqueous milieu and are incorporated into micellar nanoparticles of biocompatible Pluronic F127 (F127) after heating their solution above transition temperature, T(tr). A functional comonomer 2-(but-3-enyl)-2-oxazoline copolymerized into one of the POXs (polymer E) allows introduction of fenolic moieties and subsequent radionuclide labeling with iodine-125. Self-assembly of the polymer E with F127 leads to formation of radioactive nanoparticles with hydrodynamic diameter 20 nm in aqueous solution by heating to 37 °C. The nanoparticles are intended to be used as radioimaging tool in solid tumor diagnostics.
The reaction of α-amino-ω-methoxypoly(ethylene glycol) [M = 5000] or star α-amino-poly(ethylene glycol) [M = 20 000] with hemiesters of prednisolone dicarboxylic acids (succinic, glutaric, adipic, phthalic acid) has been used to prepare the corresponding conjugates. The rate of esterase catalyzed hydrolysis of the conjugates is controlled by the molecular mass of poly(ethylene glycol) and the length of the linker between prednisolone and poly(ethylene glycol) (τ(1/2)∼ 5-0.5 h). The enzymatic hydrolysis proceeds most rapidly at conjugates with linkers derived from adipic and phthalic acids. The synthesized conjugates form polypseudorotaxanes with α-cyclodextrin which were characterized by 2D NOESY NMR spectra, powder X-ray diffraction patterns and in one case also by STM microscopy. In the case of the polypseudorotaxane having the linker derived from adipic acid, the enzymatic release proceeds ca. five times slower in comparison with the rate of prednisolone release from the corresponding conjugate. The rate of prednisolone release from the carrier can be controlled by three factors: character of the linker between the polymeric carrier and prednisolone, the molecular mass of poly(ethylene glycol) and complex formation with α-cyclodextrin. The synthesized polypseudorotaxanes represent new promising transport systems intended for targeted release of prednisolone in transplanted liver.
Polymeric macromolecules of well-designed structures and specific properties open promising directions in the capillary entangled polymer electrophoresis. Pluronic F-127, as a thermoassociating polymer, possesses some unique properties that can be utilized in capillary entangled polymer electrophoresis of amino acids, peptides and proteins. In this study, we studied properties of Pluronic F-127 polymer as an additive to BGE for the separation of peptides and proteins. The influence of the thermoassociation on separation selectivity was studied. The addition of Pluronic caused severe instabilities of the electrical current and the signal of the UV detector. This study reveals remarkable positive effect of a low pressure applied to the inlet buffer vial during the analysis, which apparently stabilizes the electrical current and the detector signal. The effect of hydrodynamic flow induced by the pressure applied on the separation efficiency was studied and the significance of this effect was discussed. Pluronic F-127, as a representative of synthetic macromolecules, was compared with dextran, as a representative of natural polymers, in terms of separation power, selectivity and repeatability of migration times.
