Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity.

• Klíčová slova
• HPMA copolymers, biodegradable spacer, controlled drug release, drug delivery systems, pH-controlled release,
• MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• methakryláty chemie   terapeutické užití   MeSH
• nádory farmakoterapie   MeSH
• nosiče léků chemie   terapeutické užití   MeSH
• uvolňování léčiv * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• hydroxypropyl methacrylate MeSH Prohlížeč
• léky s prodlouženým účinkem MeSH
• methakryláty MeSH
• nosiče léků MeSH

In transdermal drug delivery applications uniform drug distribution and sustained release are of great importance to decrease the side effects. In this direction in the present research, vanillin crosslinked chitosan (CS) and polyvinyl alcohol (PVA) blend based matrix-type transdermal system was prepared by casting and drying of aqueous solutions for local delivery of enrofloxacin (ENR) drug. Subsequently, the properties including the morphology, chemical structure, thermal behavior, tensile strength, crosslinking degree, weight uniformity, thickness, swelling and drug release of the CS-PVA blend films before and after crosslinking were characterized. In vitro drug release profiles showed the sustained release of ENR by the incorporation of vanillin as a crosslinker into the CS-PVA polymer matrix. Furthermore, the release kinetic profiles revealed that the followed mechanism for all samples was Higuchi and the increase of vanillin concentration in the blend films resulted in the change of diffusion mechanism from anomalous transport to Fickian diffusion. Overall, the obtained results suggest that the investigated vanillin crosslinked CS-PVA matrix-type films are potential candidates for transdermal drug delivery system.

• Klíčová slova
• Chitosan, Controlled drug release, Crosslinking, Drug-polymer solubility, Solvent casting, Transdermal delivery, Vanillin,
• MeSH
• benzaldehydy MeSH
• chitosan * MeSH
• enrofloxacin MeSH
• léky s prodlouženým účinkem MeSH
• polyvinylalkohol * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzaldehydy MeSH
• chitosan * MeSH
• enrofloxacin MeSH
• léky s prodlouženým účinkem MeSH
• polyvinylalkohol * MeSH
• vanillin MeSH Prohlížeč

Thrombosis is a life-threatening pathological condition in which blood clots form in blood vessels, obstructing or interfering with blood flow. Thrombolytic agents (TAs) are enzymes that can catalyze the conversion of plasminogen to plasmin to dissolve blood clots. The plasmin formed by TAs breaks down fibrin clots into soluble fibrin that finally dissolves thrombi. Several TAs have been developed to treat various thromboembolic diseases, such as pulmonary embolisms, acute myocardial infarction, deep vein thrombosis, and extensive coronary emboli. However, systemic TA administration can trigger non-specific activation that can increase the incidence of bleeding. Moreover, protein-based TAs are rapidly inactivated upon injection resulting in the need for large doses. To overcome these limitations, various types of nanocarriers have been introduced that enhance the pharmacokinetic effects by protecting the TA from the biological environment and targeting the release into coagulation. The nanocarriers show increasing half-life, reducing side effects, and improving overall TA efficacy. In this work, the recent advances in various types of TAs and nanocarriers are thoroughly reviewed. Various types of nanocarriers, including lipid-based, polymer-based, and metal-based nanoparticles are described, for the targeted delivery of TAs. This work also provides insights into issues related to the future of TA development and successful clinical translation.

• Klíčová slova
• drug delivery, nanoparticles, plasminogen activators, thrombolytic agents, thrombosis,
• MeSH
• fibrinolytika terapeutické užití   MeSH
• hemokoagulace MeSH
• infarkt myokardu * MeSH
• léky s prodlouženým účinkem terapeutické užití   MeSH
• lidé MeSH
• trombóza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• fibrinolytika MeSH
• léky s prodlouženým účinkem MeSH

Hypoglycaemic episodes represent serious and frequent complications of type 1 and 2 diabetes. Theoretically, the risk of hypoglycaemic states can be affected by a dosage form based on a food supplement containing a delayed release formulation of glucose. The release of glucose should compensate for balance the peak effect of an antidiabetic treatment. In clinical practice, a diet with fibre and grains is recommended and patients are broadly educated in the topic of low and high glycaemic indexes to achieve the same effect. However, a precisely-timed release of carbohydrates can favourably target expected hypoglycaemia and concurrently decrease carbohydrate content. To study the possibility of preparing the dosage form with controlled-release carbohydrates, a dosage form of pellets containing four osmotically active substances coated by a membrane created of ethylcellulose was prepared. These pellets can be administered in a mixture with liquid or semisolid food. The resulting dissolution profiles for selected compositions showed that delayed release can be achieved for 120, 240 and 360min in vitro, representing an ideal delay for clinical purposes.

• Klíčová slova
• Delayed release, Glucose, Hypoglycaemia, Pellets,
• MeSH
• dítě MeSH
• glukosa chemie   MeSH
• hypoglykemie prevence a kontrola   MeSH
• lékové transportní systémy * MeSH
• léky s prodlouženým účinkem chemie   MeSH
• lidé MeSH
• rozpustnost MeSH
• uvolňování léčiv MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glukosa MeSH
• léky s prodlouženým účinkem MeSH

The aim of the study was to prepare PLGA microparticles for prolonged release of mirtazapine by o/w solvent evaporation method and to evaluate effects of PVA concentration and organic solvent choice on microparticles characteristics (encapsulation efficiency, drug loading, burst effect, microparticle morphology). Also in vitro drug release tests were performed and the results were correlated with kinetic model equations to approximate drug release mechanism. It was found that dichloromethane provided microparticles with better qualities (encapsulation efficiency 64.2%, yield 79.7%). Interaction between organic solvent effect and effect of PVA concentration was revealed. The prepared samples released the drug for 5 days with kinetics very close to that of zero order (R(2 )= 0.9549 - 0.9816). According to the correlations, the drug was probably released by a combination of diffusion and surface erosion, enhanced by polymer swelling and chain relaxation.

• Klíčová slova
• Drug release, PLGA, kinetics, solvent evaporation method,
• MeSH
• antidepresiva chemie   MeSH
• kinetika MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná chemie   MeSH
• kyselina polyglykolová chemie   MeSH
• léky s prodlouženým účinkem chemie   MeSH
• methylenchlorid chemie   MeSH
• mianserin analogy a deriváty   chemie   MeSH
• mikrosféry MeSH
• mirtazapin MeSH
• rozpouštědla chemie   MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná MeSH
• kyselina polyglykolová MeSH
• léky s prodlouženým účinkem MeSH
• methylenchlorid MeSH
• mianserin MeSH
• mirtazapin MeSH
• rozpouštědla MeSH

UNLABELLED: Eudragit® NM was investigated as a matrix former in combination with microcrystalline cellulose as an insoluble filler for preparing controlled-release tablets containing model drugs with different solubility. MATERIAL AND METHODS: Three sets of matrix tablets differing in the drug-to-filler ratio (1:1, 2:1, and 4:1) and polymer amount with diltiazem hydrochloride (freely soluble) or caffeine (sparingly soluble) were prepared. Samples were evaluated by the dissolution test at pH 6.8 corresponding to the upper part of the small intestine; the selected samples were tested at a changing pH level to better simulate in vivo conditions. RESULTS: The prepared matrix tablets fulfilled all the requirements of the European Pharmacopoeia. Tablets with Eudragit® NM showed excellent mechanical characteristics. In vitro studies showed that the set 1:1 was the most suitable for the sustained release of a freely soluble drug concerning the burst effect and the total drug amount released within 12 hours. The significant effect of the drug-to-filler ratio and polymer amount on the dissolution profile was confirmed by similarity factor analysis. A faster drug release was observed during the dissolution test within changing pH levels because of the pH-dependent solubility of diltiazem. A prolonged release of the sparingly soluble drug was not achieved, and a trend for fast disintegration was observed. CONCLUSIONS: The combination of Eudragit®NM with microcrystalline cellulose as an insoluble filler seems to be suitable only for freely soluble drugs, when the amount of the drug and the filler is similar.

• MeSH
• celulosa chemie   MeSH
• kyseliny polymethakrylové chemie   MeSH
• léky s prodlouženým účinkem chemie   MeSH
• racionální návrh léčiv * MeSH
• rozpustnost MeSH
• tablety MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• celulosa MeSH
• kyseliny polymethakrylové MeSH
• léky s prodlouženým účinkem MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• tablety MeSH

The preemergence chloroacetamide herbicide metazachlor was encapsulated in biodegradable low molecular weight poly(lactic acid) micro- and submicroparticles, and its release to the water environment was investigated. Three series of particles, S, M, and L, varying in their size (from 0.6 to 8 μm) and with various initial amounts of the active agent (5%, 10%, 20%, 30% w/w) were prepared by the oil-in-water solvent evaporation technique with gelatin as biodegradable surfactant. The encapsulation efficiencies reached were about 60% and appeared to be lower for smaller particles. Generally, it was found that the rate of herbicide release decreased with increasing size of particles. After 30 days the portions of the herbicide released for its highest loading (30% w/w) were 92%, 56%, and 34% for about 0.6, 0.8, and 8 μm particles, respectively. The release rates were also lower for lower herbicide loadings. Metazachlor release from larger particles tended to be a diffusion-controlled process, while for smaller particles the kinetics was strongly influenced by an initial burst release.

• MeSH
• acetamidy chemie   MeSH
• herbicidy chemie   MeSH
• kinetika MeSH
• kyselina mléčná chemie   MeSH
• léky s prodlouženým účinkem chemie   MeSH
• molekulová hmotnost MeSH
• polyestery MeSH
• polymery chemie   MeSH
• příprava léků metody   MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetamidy MeSH
• herbicidy MeSH
• kyselina mléčná MeSH
• léky s prodlouženým účinkem MeSH
• metazachlor MeSH Prohlížeč
• poly(lactide) MeSH Prohlížeč
• polyestery MeSH
• polymery MeSH

To employ dual advantages of emulsion and gel, a facile approach was investigated to fabricate core/shells structured hydrogel beads based on sodium alginate (SA) via Pickering emulsion template and in situ gelation. The encapsulation and controlled release behavior were further studied using lysozyme (Ly) as the model protein. The optical micrographs and SEM images indicated the SA beads could well disperse with the size about 150 μm. CaCO3 microparticles were strong adhesive onto SA gel. It showed that 96.51 ± 0.62% Ly was loaded into the hydrogel beads. The released behavior of Ly could be regulated by external pH condition, and displayed highest release rate at pH 5.0. Whereas the lowest release rate was recorded at pH 7.0. The released behavior well followed the Hixcon-Crowell model which indicated that the release mechanism of Ly followed the corrosion diffusion law. The worth-while endeavor provide an artful and facile approach using Pickering emulsion template and in situ gelation to fabricate core/shells structured SA beads with high load capacity and controlled regulation of the entrapped functional component.

• Klíčová slova
• Calcium carbonate, Controlled release, Gel, Lysozyme, Sodium alginate,
• MeSH
• algináty chemie   MeSH
• difuze MeSH
• emulze MeSH
• hydrogely chemie   MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• léky s prodlouženým účinkem * MeSH
• muramidasa chemie   MeSH
• příprava léků metody   MeSH
• roztoky MeSH
• uhličitan vápenatý chemie   MeSH
• uvolňování léčiv MeSH
• změna skupenství MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• algináty MeSH
• emulze MeSH
• hydrogely MeSH
• léky s prodlouženým účinkem * MeSH
• muramidasa MeSH
• roztoky MeSH
• uhličitan vápenatý MeSH

Polyvinyl alcohol nanofibers incorporating the wide spectrum antibiotic gentamicin were prepared by Nanospider™ needleless technology. A polyvinyl alcohol layer, serving as a drug reservoir, was covered from both sides by polyurethane layers of various thicknesses. The multilayered structure of the nanofibers was observed using scanning electron microscopy, the porosity was characterized by mercury porosimetry, and nitrogen adsorption/desorption measurements were used to determine specific surface areas. The stability of the gentamicin released from the electrospun layers was proved by high-performance liquid chromatography (HPLC) and inhibition of bacterial growth. Drug release was investigated using in vitro experiments with HPLC/MS quantification, while the antimicrobial efficacy was evaluated on Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. Both experiments proved that the released gentamicin retained its activity and showed that the retention of the drug in the nanofibers was prolonged with the increasing thickness of the covering layers.

• Klíčová slova
• drug release, electrospinning, gentamicin, morphology, multilayered structure, nanofibers,
• MeSH
• antibakteriální látky aplikace a dávkování   chemie   MeSH
• difuze MeSH
• elektrochemie metody   MeSH
• gentamiciny aplikace a dávkování   MeSH
• grampozitivní bakterie účinky léků   fyziologie   MeSH
• léky s prodlouženým účinkem aplikace a dávkování   chemie   MeSH
• nanokapsle chemie   ultrastruktura   MeSH
• rotace MeSH
• testování materiálů MeSH
• velikost částic MeSH
• viabilita buněk účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• gentamiciny MeSH
• léky s prodlouženým účinkem MeSH
• nanokapsle MeSH

• MeSH
• biokompatibilní materiály chemická syntéza   MeSH
• chemické modely MeSH
• lékové transportní systémy * MeSH
• léky s prodlouženým účinkem * MeSH
• polymery chemická syntéza   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• léky s prodlouženým účinkem * MeSH
• polymery MeSH