The incorporation of sensitive bioactive substances such as proteins or DNA into nanofibers poses a significant problem due to the toxicity of most organic solvents. The main idea of this study is to use alternating current electrospraying to create a suspension consisting of polyvinyl alcohol (PVA) capsules containing a bioactive substance dispersed in a solvent system suitable for a water-insoluble biocompatible polymer. In this suspension consisting of PVA capsules and a chloroform/ethanol mixture, poly (ε-caprolactone) (PCL) was dissolved and spun by needle-free electrospinning. The result is a fibrous PCL structure in which PVA capsules containing the bioactive agent are integrated. The PVA capsules protect the bioactive substance from the organic solvents needed to dissolve the PCL. To verify the efficacy of the capsules' protection against chloroform, the green fluorescent protein was first encapsulated into the nanofibers, followed by horseradish peroxidase. Both molecules were shown to retain their bioactivity within the nanofibers.

• Klíčová slova
• AC electrospraying, biomolecules, electrospinning, encapsulation, proteins,
• MeSH
• biokompatibilní materiály chemie   MeSH
• chloroform chemie   MeSH
• ethanol chemie   MeSH
• křenová peroxidasa chemie   metabolismus   MeSH
• nanovlákna * chemie   MeSH
• polyestery * chemie   MeSH
• polyvinylalkohol chemie   MeSH
• rozpouštědla chemie   MeSH
• tobolky chemie   MeSH
• zelené fluorescenční proteiny chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• chloroform MeSH
• ethanol MeSH
• křenová peroxidasa MeSH
• polycaprolactone MeSH Prohlížeč
• polyestery * MeSH
• polyvinylalkohol MeSH
• rozpouštědla MeSH
• tobolky MeSH
• zelené fluorescenční proteiny MeSH

OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract. METHODS: Hard gelatin capsules and DRcapsTMcapsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms. RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcapsTM capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields. CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.

• Klíčová slova
• Capsules, Coating, Immersion method, Novel approach in delayed-release dosage form with potential benefits for individual treatment, Principal component analysis,
• MeSH
• bakteriální polysacharidy chemie   MeSH
• biokompatibilní materiály chemie   MeSH
• celulosa * chemie   analogy a deriváty   MeSH
• deriváty hypromelózy chemie   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• hydrogely chemie   MeSH
• kofein chemie   aplikace a dávkování   MeSH
• kolon * metabolismus   MeSH
• kyseliny polymethakrylové chemie   MeSH
• lékové transportní systémy * metody   MeSH
• léky s prodlouženým účinkem chemie   MeSH
• polymery chemie   MeSH
• polyvinyly chemie   MeSH
• tobolky * MeSH
• uvolňování léčiv * MeSH
• želatina * chemie   MeSH
• železité sloučeniny chemie   aplikace a dávkování   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bakteriální polysacharidy MeSH
• biokompatibilní materiály MeSH
• celulosa * MeSH
• deriváty hypromelózy MeSH
• ethyl cellulose MeSH Prohlížeč
• ferric oxide MeSH Prohlížeč
• gellan gum MeSH Prohlížeč
• hydrogely MeSH
• kofein MeSH
• kyseliny polymethakrylové MeSH
• léky s prodlouženým účinkem MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• polymery MeSH
• polyvinyl acetate MeSH Prohlížeč
• polyvinyly MeSH
• tobolky * MeSH
• želatina * MeSH
• železité sloučeniny MeSH

Postmodification of alginate-based microspheres with polyelectrolytes (PEs) is commonly used in the cell encapsulation field to control microsphere stability and permeability. However, little is known about how different applied PEs shape the microsphere morphology and properties, particularly in vivo. Here, we addressed this question using model multicomponent alginate-based microcapsules postmodified with PEs of different charge and structure. We found that the postmodification can enhance or impair the mechanical resistance and biocompatibility of microcapsules implanted into a mouse model, with polycations surprisingly providing the best results. Confocal Raman microscopy and confocal laser scanning microscopy (CLSM) analyses revealed stable interpolyelectrolyte complex layers within the parent microcapsule, hindering the access of higher molar weight PEs into the microcapsule core. All microcapsules showed negative surface zeta potential, indicating that the postmodification PEs get hidden within the microcapsule membrane, which agrees with CLSM data. Human whole blood assay revealed complex behavior of microcapsules regarding their inflammatory and coagulation potential. Importantly, most of the postmodification PEs, including polycations, were found to be benign toward the encapsulated model cells.

• MeSH
• algináty * chemie   MeSH
• lidé MeSH
• mikrosféry MeSH
• myši MeSH
• polyaminy * chemie   MeSH
• polyelektrolyty * chemie   MeSH
• tobolky * chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• algináty * MeSH
• polyaminy * MeSH
• polycations MeSH Prohlížeč
• polyelektrolyty * MeSH
• tobolky * MeSH

Background and Objectives: The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Materials and Methods: Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. Results: The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for Cmax, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC0-t, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC0-∞. Conclusions: Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed.

• Klíčová slova
• bioequivalence study, dissolution, enteric coating, industrial development, omeprazole, pellets, stability study,
• MeSH
• klinické křížové studie MeSH
• lidé MeSH
• omeprazol * chemie   MeSH
• terapeutická ekvivalence MeSH
• tobolky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• omeprazol * MeSH
• tobolky MeSH

BACKGROUND: There is no single gold standard for investigation of gastrointestinal motility function. Wireless motility monitoring involves a novel concept which provides a complex information on gastrointestinal function (gastrointestinal transit time, intra-luminal pH, pressure and temperature). Gastrointestinal motility functions of experimental pigs are very similar to those of humans. That is why porcine studies have already provided suitable experimental models for several preclinical projects. AIMS: The aim of our study was to adopt methods of non-invasive wireless monitoring of gastrointestinal functions in experimental pigs. METHODS: Five experimental adult female pigs were enrolled into the study. Wireless motility capsules were delivered into the porcine stomach endoscopically. Gastrointestinal transit and intra-luminal conditions were recorded for five days. RESULTS: Records of animals provided good (3 pigs) or very good quality files (2 pigs). 31150 variables were evaluated. Mean time of the presence of capsules in the stomach was 926 ± 295 min, transfer of a capsule from the stomach into the duodenum lasted 5-34 min. Mean small intestinal transit time was 251 ± 43 min. Food intake was associated with an increase of gastric luminal temperature and a decrease of intra-gastric pressure. The highest intra-luminal pH was present in the ileum. The highest temperature and the lowest intra-luminal pressure were found in the colon. All data displayed a substantial inter-individual variability. CONCLUSIONS: This pilot study has proven that a long-term function monitoring of the gastrointestinal tract by means of wireless motility capsules in experimental pigs is feasible. However, both ketamine-based induction of general anaesthesia as well as long-lasting general anaesthesia (> 6 hours) should be avoided to prevent retention of a capsule in the porcine stomach.

• Klíčová slova
• acetylcholinesterase inhibitors, experimental pigs, gastrointestinal transit time, intra-luminal pH, oncology, pressure and temperature, toxicology, wireless capsule monitoring,
• MeSH
• dospělí MeSH
• gastrointestinální průchod * MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• pilotní projekty MeSH
• prasata MeSH
• teplota MeSH
• tobolky MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• tobolky MeSH

The restoration of mechanical properties is desired for creating the self-healing coatings with no corrosion capabilities. The encapsulation of epoxy resins is limited by various factors in urea and melamine formaldehyde microcapsules. An improved method was developed, where epoxy resin was encapsulated by individual wrapping of poly(melamine-formaldehyde) and poly(urea-formaldehyde) shell around emulsified epoxy droplets via oil-in-water emulsion polymerization method. The synthesized materials were characterized analytically. The curing of the epoxy was achieved by adding the [Ni/Co(2-MI)6].2NO3 as a latent hardener and iron acetylacetonate [Fe(acac)3] as a latent accelerator. Isothermal and non-isothermal differential scanning calorimetric analysis revealed lower curing temperature (Tonset = 116 °C) and lower activation energies (Ea ≈ 69-75 kJ/mol). The addition of microcapsules and complexes did not adversely alter the flexural strength and flexural modulus of the epoxy coatings. The adhesion strength of neat coating decreased from 6310.8 ± 31 to 4720.9 ± 60 kPa and percent healing increased from 50.83 to 67.45% in the presence of acetylacetonate complex at 10 wt% of microcapsules.

• Klíčová slova
• Adhesion strength, Epoxy resins, Flexural strength, Melamine-urea-formaldehyde, Metal imidazole complex, Self-healing,
• MeSH
• epoxidové pryskyřice * MeSH
• hydroxybutyráty * MeSH
• imidazoly MeSH
• pentanony MeSH
• tobolky MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetyl acetonate MeSH Prohlížeč
• epoxidové pryskyřice * MeSH
• hydroxybutyráty * MeSH
• imidazoly MeSH
• pentanony MeSH
• tobolky MeSH

The aim of this study was to fabricate novel microparticles (MPs) for efficient and long-term delivery of amikacin (AMI). The emulsification method proposed for encapsulating AMI employed low-molecular-weight poly(lactic acid) (PLA) and poly(lactic acid-co-polyethylene glycol) (PLA-PEG), both supplemented with poly(vinyl alcohol) (PVA). The diameters of the particles obtained were determined as less than 30 μm. Based on an in-vitro release study, it was proven that the MPs (both PLA/PVA- and PLA-PEG/PVA-based) demonstrated long-term AMI release (2 months), the kinetics of which adhered to the Korsmeyer-Peppas model. The loading efficiencies of AMI in the study were determined at the followings levels: 36.5 ± 1.5 μg/mg for the PLA-based MPs and 106 ± 32 μg/mg for the PLA-PEG-based MPs. These values were relatively high and draw parallels with studies published on the encapsulation of aminoglycosides. The MPs provided antimicrobial action against the Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae bacterial strains. The materials were also comprehensively characterized by the following methods: differential scanning calorimetry; gel permeation chromatography; scanning electron microscopy; Fourier transform infrared spectroscopy-attenuated total reflectance; energy-dispersive X-ray fluorescence; and Brunauer-Emmett-Teller surface area analysis. The findings of this study contribute toward discerning new means for conducting targeted therapy with polar, broad spectrum antibiotics.

• Klíčová slova
• amikacin encapsulation, drug delivery systems, microparticles, poly(lactic acid), targeted therapy,
• MeSH
• amikacin aplikace a dávkování   chemie   MeSH
• antibakteriální látky aplikace a dávkování   chemie   MeSH
• Escherichia coli účinky léků   MeSH
• Klebsiella pneumoniae účinky léků   MeSH
• laktáty chemie   MeSH
• mikrobiální testy citlivosti MeSH
• molekulová hmotnost MeSH
• nosiče léků chemie   MeSH
• polyestery chemie   MeSH
• polyethylenglykoly chemie   MeSH
• polyvinylalkohol chemie   MeSH
• příprava léků metody   MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• rozpustnost MeSH
• Staphylococcus aureus účinky léků   MeSH
• tobolky MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amikacin MeSH
• antibakteriální látky MeSH
• laktáty MeSH
• nosiče léků MeSH
• poly(lactic acid-ethylene glycol) MeSH Prohlížeč
• poly(lactide) MeSH Prohlížeč
• polyestery MeSH
• polyethylenglykoly MeSH
• polyvinylalkohol MeSH
• tobolky MeSH

Significant improvements in the voltammetric determination of β-carotene (BCA) have been achieved, mainly by the replacement of toxic dichloromethane with acetone and using non-mercury electrode. The respective procedure is based on anodic oxidation of BCA at a gold electrode in the disc configuration, when using square-wave voltammetry in pure acetone (99.8%) with 0.1 mol L-1 LiClO4 as the supporting electrolyte. The method comprises extraction of the analyte from the sample with acetone, thus avoiding the usually used highly toxic solvents. Analytically, it can be characterized by a linear range from 6.0 × 10-6 to 5.9 × 10-4 mol L-1 with regression equation Ipa = 0.0184c -0.1631 and correlation coefficient, R2 = 0.9998, limits of detection and quantification LOD = 1.6 × 10-6 mol L-1 and LOQ = 5.4 × 10-6 mol L-1, respectively; both being obtained at a potential step of 5 mV, with the pulse amplitude of 25 mV, and a frequency of 80 Hz. After optimization, the method was evaluated in series of analyses; namely, with two samples of vegetables and two pharmaceutical preparations (capsules), when the results could be compared to those of a reference spectrophotometric method. Due to a simple instrumentation, including sample preparation, the voltammetric method for the determination of BCA can be recommended as a quick screening assay in food and pharmaceutical analysis.

• Klíčová slova
• Food and pharmaceutical samples, Gold disk electrode, Square-wave voltammetry, β-Carotene,
• MeSH
• beta-karoten MeSH
• elektrochemie MeSH
• elektrody MeSH
• tobolky MeSH
• zelenina * MeSH
• zlato * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-karoten MeSH
• tobolky MeSH
• zlato * MeSH

BACKGROUND: Randomized controlled studies of combination therapies in rosacea are limited. OBJECTIVE: Evaluate the efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40-mg modified-release capsules (ie, 30-mg immediate-release and 10-mg delayed-release beads) (DMR) versus IVM and placebo for treatment of severe rosacea. METHODS: This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA] score, 4) to receive either IVM and DMR (combination arm) or IVM and placebo (monotherapy). RESULTS: A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (-80.3% vs -73.6% for monotherapy [P = .032]) and IGA score (P = .032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving an IGA score of 0 (11.9% vs 5.1% [P = .043]) and 100% lesion reduction (17.8% vs 7.2% [P = .006]) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index score, and ocular signs/symptoms and were well tolerated. LIMITATIONS: The duration of the study prevented evaluation of potential recurrences or further improvements. CONCLUSION: Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea.

• Klíčová slova
• clear, combination therapy, concomitant use, doxycycline, individualized treatment, ivermectin, rosacea, rosacea treatment, severe rosacea,
• MeSH
• aplikace orální MeSH
• časové faktory MeSH
• dospělí MeSH
• doxycyklin aplikace a dávkování   MeSH
• ivermektin aplikace a dávkování   MeSH
• kombinovaná farmakoterapie metody   MeSH
• kvalita života MeSH
• léky s prodlouženým účinkem aplikace a dávkování   MeSH
• lidé MeSH
• placebo aplikace a dávkování   MeSH
• pleťový krém aplikace a dávkování   MeSH
• rosacea komplikace   diagnóza   farmakoterapie   MeSH
• spokojenost pacientů MeSH
• stupeň závažnosti nemoci MeSH
• tobolky MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• klinické zkoušky, fáze IV MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• doxycyklin MeSH
• ivermektin MeSH
• léky s prodlouženým účinkem MeSH
• placebo MeSH
• tobolky MeSH

The effectiveness of cell transplantation can be improved by optimization of the transplantation site. For some types of cells that form highly oxygen-demanding tissue, e.g., pancreatic islets, a successful engraftment depends on immediate and sufficient blood supply. This critical point can be avoided when cells are transplanted into a bioengineered pre-vascularized cavity which can be formed using a polymer scaffold. In our study, we tested surface-modified poly(lactide-co-caprolactone) (PLCL) capsular scaffolds containing the pro-angiogenic factor VEGF. After each modification step (i.e., amination and heparinization), the surface properties and morphology of scaffolds were characterized by ATR-FTIR and XPS spectroscopy, and by SEM and AFM. All modifications preserved the gross capsule morphology and maintained the open pore structure. Optimized aminolysis conditions decreased the Mw of PLCL only up to 10% while generating a sufficient number of NH2 groups required for the covalent immobilization of heparin. The heparin layer served as a VEGF reservoir with an in vitro VEGF release for at least four weeks. In vivo studies revealed that to obtain highly vascularized PLCL capsules (a) the optimal VEGF dose for the capsule was 50 μg and (b) the implantation time was four weeks when implanted into the greater omentum of Lewis rats; dense fibrous tissue accompanied by vessels completely infiltrated the scaffold and created sparse granulation tissue within the internal cavity of the capsule. The prepared pre-vascularized pouch enabled the islet graft survival and functioning for at least 50 days after islet transplantation. The proposed construct can be used to create a reliable pre-vascularized pouch for cell transplantation.

• MeSH
• bioinženýrství * MeSH
• experimentální diabetes mellitus chemicky indukované   metabolismus   patologie   MeSH
• fyziologická neovaskularizace * MeSH
• injekce intraperitoneální MeSH
• krevní glukóza analýza   MeSH
• krysa rodu Rattus MeSH
• molekulární struktura MeSH
• polyestery chemie   metabolismus   MeSH
• potkani inbrední LEW MeSH
• streptozocin aplikace a dávkování   MeSH
• tobolky chemie   metabolismus   MeSH
• transplantace Langerhansových ostrůvků * MeSH
• vaskulární endoteliální růstové faktory chemie   metabolismus   MeSH
• velikost částic MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• krevní glukóza MeSH
• poly(lactide) MeSH Prohlížeč
• polyestery MeSH
• streptozocin MeSH
• tobolky MeSH
• vaskulární endoteliální růstové faktory MeSH