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

After patent protection of original brand is over, there are a lot of generic products occurring on the pharmaceutical market. It may be the way to reduce the price, but on the other hand, one should expect the same quality and almost identity with original brand, because the development of generic drugs is based on pharmacological properties of the original brand. The aim of this study was to compare the similarity of two products with controlled release of felodipine--generic product Presid and original brand Plendil--which are commercially available in Czech Republic, based on in vitro dissolution testing. The dissolution test in three dissolution media of increasing pH (1.2, 4.5, and 6.5) for the simulation of physiological pH within the gastrointestinal tract confirmed controlled release of felodipine from the original product Plendil ER 5 mg and Plendil ER 10 mg during the period of 24 hours. The release of felodipine from generic products Presid 5 mg and Presid 10 mg was not controlled for 24 hours as it is indicated in the information leaflet. In the generic products, felodipine release was controlled just for 12 or 18 hours and in this respect did not show similarity with the original brand. Since patients take the drug just once a day in the morning, the controlled release of felodipine, which lasts only 12 to 18 hours, can cause insufficient blood pressure control especially in the most critical morning hours and higher cardiovascular risk.

• MeSH
• antihypertenziva aplikace a dávkování   farmakokinetika   MeSH
• blokátory kalciových kanálů aplikace a dávkování   farmakokinetika   MeSH
• časové faktory MeSH
• felodipin aplikace a dávkování   farmakokinetika   MeSH
• generika aplikace a dávkování   farmakokinetika   MeSH
• hypertenze farmakoterapie   MeSH
• interpretace statistických dat MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• rozpustnost MeSH
• spektrofotometrie ultrafialová MeSH
• techniky in vitro MeSH
• terapeutická ekvivalence MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antihypertenziva MeSH
• blokátory kalciových kanálů MeSH
• felodipin MeSH
• generika MeSH
• léky s prodlouženým účinkem MeSH

The pharmacokinetics and beta-adrenoceptor blocking effects of conventional and sustained-release metipranolol have been studied in 6 healthy male volunteers given a single oral dose of 40 mg. Plasma drug concentrations determined by TLC and a radioreceptor assay, and the inhibition of exercise-induced tachycardia, were monitored for 48 h. Relevant amounts of active metabolites other than deacetylmetipranolol were not found. Compared to conventionally formulated metipranolol, the controlled-release product had a prolonged mean residence time (10.7 vs 5.5 h), the peak drug concentration was halved and the time to peak drug concentrations was delayed. Relatively constant plasma concentrations (cideal = 6.5 ng/ml) and a clinically significant reduction of exercise-induced tachycardia were maintained throughout a 24 h dosing interval. An individual deacetylmetipranolol plasma concentration-effect relationship was evaluated using the Emax model. Mean parameters were Emax 26% and C50 2.9 ng/ml.

• MeSH
• beta blokátory MeSH
• chromatografie na tenké vrstvě MeSH
• dospělí MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• metipranolol aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• propanolaminy farmakokinetika   MeSH
• radioligandová zkouška MeSH
• srdeční frekvence účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• beta blokátory MeSH
• léky s prodlouženým účinkem MeSH
• metipranolol MeSH
• propanolaminy 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

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

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

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

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

A novel class of anti-cancer therapeutics - polymeric conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers and doxorubicin with pH-controlled release of the drug - is highly efficient in killing tumor cells in vitro and is potent in eradicating growing tumors in vivo. Moreover, in comparison with low-molecular-weight drugs, the macromolecular therapeutics show decreased acute as well as delayed adverse side-toxicity. More importantly, the polymeric conjugates trigger the onset of specific anti-tumor immune response and this anti-tumor immunity can be transferred with splenocytes to naïve recipients. In other terms, chemotherapy based on conjugates of HPMA copolymer with doxorubicin possesses immunomodulating properties. This finding might also have wider implications for the management of relapsing tumors in human patients.

• MeSH
• akrylamidy chemická syntéza   farmakologie   MeSH
• antitumorózní látky chemická syntéza   farmakologie   MeSH
• doxorubicin analogy a deriváty   chemická syntéza   farmakologie   MeSH
• experimentální nádory imunologie   prevence a kontrola   MeSH
• galaktosamin chemická syntéza   farmakologie   MeSH
• imunoterapie adoptivní * MeSH
• inhibiční koncentrace 50 MeSH
• injekce subkutánní MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny polymethakrylové chemická syntéza   farmakologie   MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• slezina cytologie   imunologie   transplantace   MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• antitumorózní látky MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• galaktosamin MeSH
• HPMA coploymer-doxorubicin-galactosamine MeSH Prohlížeč
• kyseliny polymethakrylové MeSH
• léky s prodlouženým účinkem MeSH