The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.
- MeSH
- 3D tisk * MeSH
- aplikace kožní MeSH
- imichimod * chemie aplikace a dávkování MeSH
- jehly * MeSH
- kožní absorpce MeSH
- kůže metabolismus MeSH
- mikroinjekce přístrojové vybavení MeSH
- nanočástice * chemie aplikace a dávkování MeSH
- polyethylenglykoly chemie aplikace a dávkování MeSH
- povidon chemie MeSH
- rozpustnost * MeSH
- systémy cílené aplikace léků přístrojové vybavení MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In this work, the solid-liquid equilibrium (SLE) curve for ten active pharmaceutical ingredients (APIs) with the polymer polyvinylpyrrolidone (PVP) K12 was purely predicted using the Conductor-like Screening Model for Real Solvents (COSMO-RS). In particular, two COSMO-RS-based strategies were followed (i.e., a traditional approach and an expedited approach), and their performances were compared. The veracity of the predicted SLE curves was assessed via a comparison with their respective SLE dataset that was obtained using the step-wise dissolution (S-WD) method. Overall, the COSMO-RS-based API-PVP K12 SLE curves were in satisfactory agreement with the S-WD-based data points. Of the twenty predicted SLE curves, only two were found to be in strong disagreement with the corresponding experimental values (both modeled using the expedited approach). Hence, it was recommended to use the traditional approach when predicting the API-polymer SLE curve. At the present moment, COSMO-RS may be an effective computational tool for the expeditious screening of API-polymer compatibility, particularly in the case of promising novel APIs, for which experimental datasets are likely limited or non-existent.
Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 μg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α: 5.7 ± 4.3 min) and a slower elimination phase (t1/2β: 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.
- MeSH
- benzalkoniové sloučeniny farmakokinetika chemie MeSH
- intravenózní podání * MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- povidon * chemie MeSH
- quercetin * farmakokinetika analogy a deriváty aplikace a dávkování chemie MeSH
- rozpustnost * MeSH
- voda * chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR15 min) and 60 min (COMDR60 min) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR15 min (R2 = 0.82 and Q2 = 0.77) and COMDR60 min (R2 = 0.87 and Q2 = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R2 = 0.83 (COMDR15 min) and R2 = 0.84 (COMDR60 min). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD6.5 value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.
There is a growing interest in using deep eutectic solvents (DES) as a pharmaceutical delivery system for poorly water-soluble compounds. To reduce the risk of drug precipitation following oral administration, this study addresses the hypothesis that directly including a polymeric precipitation inhibitor (PI) in a DES mixture could obtain a polymer-embedded deep eutectic system (PEDES) as a novel bio-enabling formulation principle. Following broad formulation screening, a PEDES embedding 15% w/w of polyvinyl pyrrolidone K30 (PVP) in L-carnitine:ethylene glycol (1:4, molar ratio) DES was successfully formulated as a supersaturating formulation using indomethacin as model compound. The drug solubility of 175.6 mg/mL obtained in DES was remarkably high, and upon release (phosphate buffer, pH 6.5) a maximum supersaturation factor of 9.8 was recorded, whereby the release kinetics displayed a suitable "parachute effect". The formulation was further characterized to include a molecular dynamics simulation. It can be concluded that PEDES appears to be a viable novel formulation approach, setting solid grounds for further research to assess the full potential of this novel type of supersaturating drug delivery system.
The aim of this study was to investigate the molecular structures of tadalafil solid dispersions prepared by different techniques and further to relate them to surface free energy information indicating the final amorphousness of the product. Thus, we tried to complement the existing knowledge of solid dispersion formation. Poorly water-soluble tadalafil was combined with different polymers, i.e. Kollidon® 12 PF, Kollidon® VA 64 and Soluplus®, to form model systems. To assess the extent of drug-polymer miscibility, we studied model solid dispersion surface energy using inverse gas chromatography and phase micro-structure using confocal Raman microscopy. The selection of the preparation method was found to play a crucial role in the molecular arrangement of the incorporated drug and the polymer in resulting solid dispersion. Our results showed that a lower surface free energy indicated the formation of a more homogeneous solid dispersion. Conversely, a higher surface free energy corresponded to the heterogeneous systems containing tadalafil amorphous clusters that were captured by Raman mapping. Thus, we successfully introduced a novel evaluation approach of the drug molecular arrangement in solid dispersions that is especially useful for examining the miscibility of the components when the conventional characterizing techniques are inconclusive or yield variable results.
- MeSH
- chromatografie plynová MeSH
- polymery * chemie MeSH
- povidon * chemie MeSH
- rozpustnost MeSH
- tadalafil chemie MeSH
- Publikační typ
- časopisecké články MeSH
The use of noble metal nanoparticles in biomedical and biotechnological applications is nowadays well established. Particularly, silver nanoparticles (AgNPs) were proven to be effective for instance as a biocide agent. They also find applications in tumor therapies and sensing applications being encouraging tools for in-vivo imaging. In this framework, whenever they are in contact with living systems, they are rapidly coated by a protein corona thereby influencing a variety of biological events including cellular uptake, blood circulation lifetime, cytotoxicity and, ultimately, the therapeutic effect. Taking these considerations into account, we have explored the behavior of polymer-coated AgNPs in model protein environments focusing on the self-development of protein coronas. The polymers polyethyleneimine (PEI), polyvinylpyrrolidone (PVP) and poly(2-vinyl pyridine)-b-poly(ethylene oxide) (PEO-b-P2VP) were used as stabilizing agents. The chemical nature of the polymer capping remarkably influences the behavior of the hybrid nanomaterials in protein environments. The PEO-b-P2VP and PVP-stabilized AgNPs are essentially inert to the model proteins adsorption. On the other hand, the PEI-stabilized AgNPs interact strongly with bovine serum albumin (BSA). Nevertheless, the same silver colloids were evidenced to be stable in IgG and lysozyme environments. The BSA adsorption into the PEI-stabilized AgNPs is most probably driven by hydrogen bonding and van der Waals interactions as suggested by isothermal titration calorimetry data. The development of protein coronas around the AgNPs may have relevant implications in a variety of biological events. Therefore, further investigations are currently underway to evaluate the influence of its presence on the cytotoxicity, hemolytic effects and biocide properties of the produced hybrid nanomaterials.
- MeSH
- adsorpce MeSH
- dynamický rozptyl světla MeSH
- fluorescenční spektrometrie MeSH
- kalorimetrie MeSH
- koloidy chemie MeSH
- kur domácí MeSH
- nanočástice ultrastruktura MeSH
- polyethylenimin chemie MeSH
- polymery chemie MeSH
- povidon chemie MeSH
- proteinová korona chemie MeSH
- sérový albumin hovězí chemie MeSH
- skot MeSH
- spektrofotometrie ultrafialová MeSH
- stříbro chemie MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tungsten oxide-based bulk and nanocrystalline materials are widely used as photocatalytic and photo- and electrochromic materials, as well as materials for biomedical applications. In our work, we focused our attention on the effect of sodium cations on the structure and photochromic properties of the WO3@PVP aqueous sols. To establish the effect, the sols were synthesized by either simple pH adjusting of sodium or ammonium tungstates' solutions, or using an ion exchange technique to remove the cations from the materials to the greatest possible extent. We showed that the presence of sodium cations in WO3@PVP favors the formation of reduced tungsten species (W+5) upon UV irradiation of the materials, strongly affecting their photochromic and photocatalytic properties. The pronounced photoreductive properties of WO3@PVP sols in photocatalytic reactions were demonstrated. Due to photoreductive properties, photochromic sols of tungsten oxide can act as effective photoprotectors in photooxidation processes. We believe that our work provides a considerable contribution to the elucidation of photochromic and redox phenomena in WO3-based materials.
- MeSH
- difrakce rentgenového záření MeSH
- fotochemické procesy MeSH
- katalýza MeSH
- kationty MeSH
- koncentrace vodíkových iontů MeSH
- maloúhlový rozptyl MeSH
- molekulární struktura MeSH
- nanočástice chemie MeSH
- oxidy chemie MeSH
- povidon chemie MeSH
- sodík chemie MeSH
- ultrafialové záření MeSH
- velikost částic MeSH
- wolfram chemie MeSH
- Publikační typ
- časopisecké články MeSH
This paper describes a potential environmental problem closely linked with the global production of water-soluble polymers such as polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Both polymers make up the components of a multitude of products commonly utilized by industries and households. Hence, such a widespread use of PVA and PVP in the industrial sector and among consumers (the concentration of PVP in urban wastewater is approximately 7 mg/L) could pose a considerable problem, particularly to the environment. To this end, many publications have recently highlighted the poor biodegradability of PVA, in principle influenced by numerous biotic and abiotic factors. Facts published on the environmental fate of PVP have been scant, basically reporting that it is a biologically resistant polymer. As a result, the commercially produced water-soluble polymers of PVA and PVP are essentially non-biodegradable and possess the capacity to accumulate in virtually all environmental media. Consequently, there is a chance of heightened risk to the very environmental constituents in which PVA and PVP accumulate, depending on the routes of entry and transformation processes underway in such constituents of the ecosystem. This assumption is confirmed by the findings of initial research, which is worrying. Herein, PVA was detected in a soil environment, while a relatively high concentration of PVP was found in river water. A review of the literature was conducted to summarize the current state of knowledge concerning the fate of PVA and PVP in various environments, thereby also discerning potential solutions to tackle such dangers. This paper proposes methods to enhance the biodegradability of materials containing such materials; for PVA this means utilizing a suitable polysaccharide, whereas for PVP this pertains to actuating applications that induce substances to degrade. Accordingly, while it is understandable that this work cannot fully address all the issues associated with polymeric xenobiotics, it can still serve as a guide to discerning an economically viable solution, and provide a foundation for further research.
In many fish species, sperm cryopreservation has deleterious effects and leads to a significant decrease in spermatozoa viability. However, the effect of cryopreservation on sperm cells that survive this process and are still viable is not fully understood. The objective of this study was to compare the viability and proteomes of fresh and cryopreserved sterlet (Acipenser ruthenus) sperm samples before and after live-dead cell separation using Percoll density gradient centrifugation. Both fresh and cryopreserved sperm samples were divided into two groups (with or without application of Percoll separation). At each step of the experiment, sperm quality was evaluated by video microscopy combined with integrated computer-assisted sperm analysis software and flow cytometry for live-dead sperm viability analysis. Sperm motility and the percentage of live cells were reduced in the cryopreserved group compared to the fresh group from 89% to 33% for percentage of motility and from 96% to 70% for live cells. Straight line velocity and linearity of track were significantly lower in cryopreserved samples than in those separated by Percoll before and after cryopreservation. However, the percentages of motile and live spermatozoa were higher than 90% in samples subjected to Percoll separation. Proteomic analysis of spermatozoa by two-dimensional differences in-gel electrophoresis coupled with matrix-assisted laser-desorption/ionization time-of-flight/time-of-flight mass spectrometry revealed that 20 protein spot abundances underwent significant changes in cryopreserved samples compared to fresh ones. However, only one protein spot was significantly altered when samples before and after cryopreservation followed by Percoll separation were compared. Thus, the results of this study show that cryopreservation leads to minimal proteomic changes in the spermatozoa population, retaining high motility and viability parameters. The results also suggest that global differences in protein profiles between unselected fresh and cryopreserved samples are mainly due to protein loss or changes in the lethal and sublethal damaged cell subpopulations.
- MeSH
- centrifugace - gradient hustoty metody MeSH
- kryoprezervace metody MeSH
- motilita spermií fyziologie MeSH
- oxid křemičitý chemie MeSH
- povidon chemie MeSH
- proteomika MeSH
- ryby fyziologie MeSH
- spermie fyziologie MeSH
- uchování spermatu metody MeSH
- viabilita buněk fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
