Strict medication adherence, which reflects the process by which patients take their medication as prescribed, is crucial for the use of direct oral anticoagulants (DOACs). Therefore, technological devices may serve as promising tools for assessing adherence. We aimed to systematically review the literature focusing on electronically monitored adherence (EMA) to DOACs. All studies indexed in EMBASE, Cochrane Library, MEDLINE, Scopus, and Web of Science from inception until September 1, 2023, were searched. Original studies targeting the query topics were included, findings were categorized and narratively synthetized. Adherence data, including the quality of data reporting bias, were evaluated using the EMERGE guideline. The review protocol was registered in the PROSPERO database (ID CRD42023441161). Out of the 5911 potential hits, 19 articles, comprising 15 research studies, were identified. These studies enrolled 4163 patients (median 72.1 years; 57.9% males), usually chronically treated with DOACs for atrial fibrillation. EMA was measured in 3451 patients by seven different devices from eight manufacturers; the median population tracked with electronic monitoring was 56 patients over 5 months per study. Observational studies resulted in 88.6% and interventional studies resulted in 92.5% of EMA to DOACs, mostly monitoring regimen and taking adherence. Two studies reported high-quality adherence data, whereas 11 reported low-quality adherence data. The item described in the EMERGE guideline as affecting adherence by measurement method, as appropriate, has rarely been addressed. This review broadens the understanding of the overall high EMA to DOACs reported across various study populations and designs. Furthermore, due to the identified gaps in current literature, it highlights the pressing need for standardized methodologies and improved adherence reporting. This study was supported by the GAUK 328322 and SVV 220665.
- Klíčová slova
- anticoagulants, atrial fibrillation, bias, electronics, implementation, medication adherence,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Stilbenes in food and medicinal plants have been described as potent antiphlogistic and antioxidant compounds, and therefore, they present an interesting potential for the development of dietary supplements. Among them, macasiamenene F (MF) has recently been shown to be an effective anti-inflammatory and cytoprotective agent that dampens peripheral and CNS inflammation in vitro. Nevertheless, this promising molecule, like other stilbenes and a large percentage of drugs under development, faces poor water solubility, which results in trickier in vivo administration and low bioavailability. With the aim of improving MF solubility and developing a form optimized for in vivo administration, eight types of conventional liposomal nanocarriers and one type of PEGylated liposomes were formulated and characterized. In order to select the appropriate form of MF encapsulation, the safety of MF liposomal formulations was evaluated on THP-1 and THP-1-XBlue-MD2-CD14 monocytes, BV-2 microglia, and primary cortical neurons in culture. Furthermore, the cellular uptake of liposomes and the effect of encapsulation on MF anti-inflammatory effectiveness were evaluated on THP-1-XBlue-MD2-CD14 monocytes and BV-2 microglia. MF (5 mol %) encapsulated in PEGylated liposomes with an average size of 160 nm and polydispersity index of 0.122 was stable, safe, and the most promising form of MF encapsulation keeping its cytoprotective and anti-inflammatory properties.
- Publikační typ
- časopisecké články MeSH
The direct tailoring of the size, composition, or number of layers belongs to the advantages of 3D printing employment in producing orodispersible films (ODFs) compared to the frequently utilized solvent casting method. This study aimed to produce porous ODFs as a substrate for medicated ink deposited by a 2D printer. The innovative semi-solid extrusion 3D printing method was employed to produce multilayered ODFs, where the bottom layer assures the mechanical properties. In contrast, the top layer provides a porous structure for ink entrapment. Hydroxypropyl methylcellulose and polyvinyl alcohol were utilized as film-forming polymers, glycerol as a plasticizer, and sodium starch glycolate as a disintegrant in the bottom matrix. Several porogen agents (Aeroperl® 300, Fujisil®, Syloid® 244 FP, Syloid® XDP 3050, Neusilin® S2, Neusilin® US2, and Neusilin® UFL2) acted as porosity enhancers in the two types of top layer. ODFs with satisfactory disintegration time were prepared. The correlation between the porogen content and the mechanical properties was proved. A porous ODF structure was detected in most samples and linked to the porogen content. SSE 3D printing represents a promising preparation method for the production of porous ODFs as substrates for subsequent drug deposition by 2D printing, avoiding the difficulties arising in casting or printing medicated ODFs directly.
- Klíčová slova
- 3D print, fast dissolving films, individualized therapy, inkjet print, oral films, porous films,
- Publikační typ
- časopisecké články MeSH
The growing need for processing natural lipophilic and often volatile substances such as thymol, a promising candidate for topical treatment of intestinal mucosa, led us to the utilization of solid-state nuclear magnetic resonance (ss-NMR) spectroscopy for the rational design of enteric pellets with a thymol self-emulsifying system (SES). The SES (triacylglycerol, Labrasol®, and propylene glycol) provided a stable o/w emulsion with particle size between 1 and 7 µm. The ex vivo experiment confirmed the SES mucosal permeation and thymol delivery to enterocytes. Pellets W90 (MCC, Neusilin®US2, chitosan) were prepared using distilled water (90 g) by the M1−M3 extrusion/spheronisation methods varying in steps number and/or cumulative time. The pellets (705−740 µm) showed mostly comparable properties—zero friability, low intraparticular porosity (0−0.71%), and relatively high density (1.43−1.45%). They exhibited similar thymol release for 6 h (burst effect in 15th min ca. 60%), but its content increased (30−39.6 mg/g) with a shorter process time. The M3-W90 fluid-bed coated pellets (Eudragit®L) prevented undesirable thymol release in stomach conditions (<10% for 3 h). A detailed, ss-NMR investigation revealed structural differences across samples prepared by M1−M3 methods concerning system stability and internal interactions. The suggested formulation and methodology are promising for other lipophilic volatiles in treating intestinal diseases.
- Klíčová slova
- ex vivo testing, rational design, self-emulsifying pellet, solid-state NMR, structure, thymol,
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- food allergy, immunotherapy and tolerance induction, next-generation AIT,
- MeSH
- alergeny aplikace a dávkování imunologie MeSH
- aplikace slizniční MeSH
- imunologická tolerance MeSH
- lékové transportní systémy MeSH
- ovalbumin aplikace a dávkování imunologie MeSH
- prasata MeSH
- sublinguální imunoterapie metody MeSH
- ústní spodina MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alergeny MeSH
- ovalbumin MeSH
Microparticles are widely used in myriad fields such as pharmaceuticals, foods, cosmetics, and other industrial fields. Compared with traditional methods for synthesizing microparticles, microfluidic techniques provide very powerful platforms for creating highly controllable emulsion droplets as templates for fabricating uniform microparticles with advanced structures and functions. Microfluidic techniques can generate emulsion droplets with precisely controlled size, shape, and composition. A more precise preparation process brings an effective tool to control the release profile of the drug and introduces an easily accessible reproducibility. The paper gives information about basic droplet-based set-ups and examples of attainable microparticle types preparable by this method.
- Klíčová slova
- PDMS, microchannels, microfluidic technique, microparticles, solvent evaporation method,
- MeSH
- emulze MeSH
- mikrofluidika * MeSH
- mikrofluidní analytické techniky * MeSH
- reprodukovatelnost výsledků MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- emulze MeSH
Microparticles are widely used in myriad fields such as pharmaceuticals, foods, cosmetics, and other industrial fields. Compared with traditional methods for synthesizing microparticles, microfluidic techniques provide very powerful platforms for creating highly controllable emulsion droplets as templates for fabricating uniform microparticles with advanced structures and functions. Microfluidic techniques can generate emulsion droplets with precisely controlled size, shape, and composition. A more precise preparation process brings an effective tool to control the release profile of the drug and introduces an easily accessible reproducibility. The paper gives information about basic droplet-based set-ups and examples of attainable microparticle types preparable by this method.
- Klíčová slova
- PDMS, microchannels, microfluidic technique, microparticles, solvent evaporation method,
- MeSH
- emulze MeSH
- mikrofluidika * MeSH
- mikrofluidní analytické techniky * MeSH
- reprodukovatelnost výsledků MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- emulze MeSH
Hydroxypropylmethylcellulose (HPMC), also known as Hypromellose, is a traditional pharmaceutical excipient widely exploited in oral sustained drug release matrix systems. The choice of numerous viscosity grades and molecular weights available from different manufacturers provides a great variability in its physical-chemical properties and is a basis for its broad successful application in pharmaceutical research, development, and manufacturing. The excellent mucoadhesive properties of HPMC predetermine its use in oromucosal delivery systems including mucoadhesive tablets and films. HPMC also possesses desirable properties for formulating amorphous solid dispersions increasing the oral bioavailability of poorly soluble drugs. Printability and electrospinnability of HPMC are promising features for its application in 3D printed drug products and nanofiber-based drug delivery systems. Nanoparticle-based formulations are extensively explored as antigen and protein carriers for the formulation of oral vaccines, and oral delivery of biologicals including insulin, respectively. HPMC, being a traditional pharmaceutical excipient, has an irreplaceable role in the development of new pharmaceutical technologies, and new drug products leading to continuous manufacturing processes, and personalized medicine. This review firstly provides information on the physical-chemical properties of HPMC and a comprehensive overview of its application in traditional oral drug formulations. Secondly, this review focuses on the application of HPMC in modern pharmaceutical technologies including spray drying, hot-melt extrusion, 3D printing, nanoprecipitation and electrospinning leading to the formulation of printlets, nanoparticle-, microparticle-, and nanofiber-based delivery systems for oral and oromucosal application. Hypromellose is an excellent excipient for formulation of classical dosage forms and advanced drug delivery systems. New methods of hypromellose processing include spray draying, hot-melt extrusion, 3D printing, and electrospinning.
- Klíčová slova
- 3D printing, Amorphous solid dispersion, Continuous manufacturing, Controlled release, Matrix tablet, Mucoadhesive formulation,
- MeSH
- deriváty hypromelózy MeSH
- farmaceutická technologie * MeSH
- pomocné látky * MeSH
- příprava léků MeSH
- rozpustnost MeSH
- tablety MeSH
- uvolňování léčiv MeSH
- viskozita MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- deriváty hypromelózy MeSH
- pomocné látky * MeSH
- tablety MeSH
Development of tools for direct thrombus imaging represents a key step for diagnosis and treatment of stroke. Nanoliposomal carriers of contrast agents and thrombolytics can be functionalized to target blood thrombi by small protein binders with selectivity for fibrin domains uniquely formed on insoluble fibrin. We employed a highly complex combinatorial library derived from scaffold of 46 amino acid albumin-binding domain (ABD) of streptococcal protein G, and ribosome display, to identify variants recognizing fibrin cloth in human thrombus. We constructed a recombinant target as a stretch of three identical fibrin fragments of 16 amino acid peptide of the Bβ chain fused to TolA protein. Ribosome display selection followed by large-scale Enzyme-Linked ImmunoSorbent Assay (ELISA) screening provided four protein variants preferentially binding to insoluble form of human fibrin. The most specific binder variant D7 was further modified by C-terminal FLAG/His-Tag or double His-tag for the attachment onto the surface of nanoliposomes via metallochelating bond. D7-His-nanoliposomes were tested using in vitro flow model of coronary artery and their binding to fibrin fibers was demonstrated by confocal and electron microscopy. Thus, we present here the concept of fibrin-targeted binders as a platform for functionalization of nanoliposomes in the development of advanced imaging tools and future theranostics.
- Klíčová slova
- ABD scaffold, binding protein, combinatorial library, fibrin, fibrinogen Bβ chain, liposome, metallochelation, thrombus imaging, thrombus targeting,
- Publikační typ
- časopisecké články MeSH
Currently, the method of external ionic gelation for the preparation of alginate particles is successfully used not only in the field of pharmacy and medicine, but also especially in the field of biotechnology. Therefore, the preparation of alginate particles and their subsequent evaluation using principal component analysis was the key task of our experiment. To optimize this method, we focused on the evaluation of the effect of formulation (the polymer concentration, the hardening solution concentration) and process parameters (the outer diameter of the injection needle) on the properties of the resulting beads (yield, sphericity factor, equivalent diameter and swelling capacity at pH 6). Using multivariate data analysis, the major influence on the resulting properties of the prepared particles was confirmed only in sodium alginate concentration. Obtained results verified the reliable and safe potential of the external ionic gelation for preparation alginate-based particulate dosage forms.
- Klíčová slova
- copper ions, evaluation of the particulate dosage form, external ionic gelation, hydrogel particles, principal component analysis, sodium alginate,
- MeSH
- algináty chemie MeSH
- analýza hlavních komponent MeSH
- měď chemie MeSH
- polymery * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- algináty MeSH
- měď MeSH
- polymery * MeSH
