BACKGROUND: Hyperkalemia (HK) is associated with suboptimal renin-angiotensin system (RAS) inhibitor and mineralocorticoid receptor antagonist (MRA) use in heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study sought to assess characteristics and RAS inhibitor/MRA use in patients receiving patiromer during the DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) run-in phase. METHODS: Patients with HFrEF and HK or past HK entered a run-in phase of ≤12 weeks with patiromer-facilitated RAS inhibitor/MRA optimization to achieve ≥50% recommended RAS inhibitor dose, 50 mg/d MRA, and normokalemia. Patients achieving these criteria (randomized group) were compared with the run-in failure group (patients not meeting the randomization criteria). RESULTS: Of 1,038 patients completing the run-in, 878 (84.6%) were randomized and 160 (15.4%) were run-in failures. Overall, 422 (40.7%) had HK entering run-in with a similar frequency in the randomized and run-in failure groups (40.3% vs 42.5%; P = 0.605). From start to the end of run-in, in the randomized group, an increase was observed in target RAS inhibitor and MRA use in patients with HK (RAS inhibitor: 76.8% to 98.6%; MRA: 35.9% to 98.6%) and past HK (RAS inhibitor: 60.5% to 98.1%; MRA: 15.6% to 98.7%). Despite not meeting the randomization criteria, an increase after run-in was observed in the run-in failure group in target RAS inhibitor (52.5% to 70.6%) and MRA use (15.0% to 48.1%). This increase was observed in patients with HK (RAS inhibitor: 51.5% to 64.7%; MRA: 19.1% to 39.7%) and past HK (RAS inhibitor: 53.3% to 75.0%; MRA: 12.0% to 54.3%). CONCLUSIONS: In patients with HFrEF and HK or past HK receiving suboptimal RAS inhibitor/MRA therapy, RAS inhibitor/MRA optimization increased during patiromer-facilitated run-in.

• Klíčová slova
• heart failure, hyperkalemia, mineralocorticoid receptor antagonists, patiromer, renin–angiotensin system inhibitors,
• MeSH
• antagonisté mineralokortikoidních receptorů * terapeutické užití   MeSH
• antagonisté receptorů pro angiotenzin terapeutické užití   MeSH
• hyperkalemie * farmakoterapie   krev   MeSH
• inhibitory ACE terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymery * terapeutické užití   MeSH
• renin-angiotensin systém účinky léků   MeSH
• senioři MeSH
• srdeční selhání * farmakoterapie   MeSH
• tepový objem účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté mineralokortikoidních receptorů * MeSH
• antagonisté receptorů pro angiotenzin MeSH
• inhibitory ACE MeSH
• patiromer MeSH Prohlížeč
• polymery * MeSH

Chronic inflammatory diseases such as rheumatoid arthritis represent a substantial socio-economic impact and have a high prevalence in the modern world. Nano-sized polymer therapeutics have shown suitable characteristics for becoming the next generation of anti-inflammatory nanomedicines. Here, we present biocompatible and stimuli-sensitive N-(2-hydroxypropyl)methacrylamide based polymer conjugates with the anti-inflammatory drug dexamethasone (DEX), which has been tailored for prolonged blood circulation, enhanced inflammatory site accumulation, site-specific drug release and subsequent elimination of the carrier via urine excretion. The hydrodynamic size of novel polymer-DEX nanomedicine was adjusted to prolong its blood circulation whilst maintaining the renal excretability of the polymer carrier after drug release in inflamed tissue. The therapeutic efficacy of the studied polymer nanomedicines was evaluated in a model of dissipated chronic arthritis, i.e. collagen II-induced arthritis, in mice. The pH-sensitive drug attachment enabled enhanced blood circulation with minimal systemic drug release, as well as rapid drug activation in affected joints. Importantly, unlike free DEX, the polymer nanomedicines were able to diminish joint inflammation and arthritis-induced bone damage - even at a reduced dosing regimen - as evaluated by micro computed tomography (micro-CT).

• Klíčová slova
• Collagen II-induced arthritis, Dexamethasone, Drug delivery, HPMA, Inflammation, Passive targeting, Polymer conjugate,
• MeSH
• antiflogistika terapeutické užití   MeSH
• artritida experimentální * diagnostické zobrazování   farmakoterapie   MeSH
• myši MeSH
• nanomedicína MeSH
• polymery terapeutické užití   MeSH
• rentgenová mikrotomografie MeSH
• revmatoidní artritida * diagnostické zobrazování   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika MeSH
• polymery MeSH

In the present Special Issue "Functional Nanomaterials and Polymer Nanocomposites: Current Uses and Potential Applications", two review articles and nine original research articles are published [...].

• MeSH
• nanokompozity * MeSH
• polymery * terapeutické užití   MeSH
• Publikační typ
• úvodníky MeSH
• Názvy látek
• polymery * MeSH

Fabrication of an appropriate skin scaffold needs to meet several standards related to the mechanical and biological properties. Fully natural/green scaffolds with acceptable biodegradability, biocompatibility, and physiological properties quite often suffer from poor mechanical properties. Therefore, for appropriate skin tissue engineering and to mimic the real functions, we need to use synthetic polymers and/or additives as complements to green polymers. Green nanocomposites (either nanoscale natural macromolecules or biopolymers containing nanoparticles) are a class of scaffolds with acceptable biomedical properties window (drug delivery and cardiac, nerve, bone, cartilage as well as skin tissue engineering), enabling one to achieve the required level of skin regeneration and wound healing. In this review, we have collected, summarized, screened, analyzed, and interpreted the properties of green nanocomposites used in skin tissue engineering and wound dressing. We particularly emphasize the mechanical and biological properties that skin cells need to meet when seeded on the scaffold. In this regard, the latest state of the art studies directed at fabrication of skin tissue and bionanocomposites as well as their mechanistic features are discussed, whereas some unspoken complexities and challenges for future developments are highlighted.

• Klíčová slova
• biological properties, biomaterials, bionanocomposites, green nanocomposites, mechanical properties, skin tissue engineering,
• MeSH
• biokompatibilní materiály terapeutické užití   MeSH
• hydrogely MeSH
• nanokompozity * terapeutické užití   MeSH
• polymery terapeutické užití   MeSH
• tkáňové inženýrství * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• hydrogely MeSH
• polymery MeSH

Obstructed blood flow and erratic blood supply in the tumor region attenuate the distribution and accumulation of nanomedicines in the tumor. Therefore, improvement of these conditions is crucial for efficient drug delivery. In this study, we designed and synthesized a novel N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer conjugate of BK, which possessed adequate systemic stability and tumor-selective action required to improve the accumulation of nanomedicines in the tumor. Levulinoyl-BK (Lev-BK) was conjugated to an HPMA-based polymer via an acid-cleavable hydrazone bond (P-BK). An acid-responsive release of Lev-BK from P-BK was observed, and P-BK alone after intradermal application showed below 10% of the BK activity, thus proving a reduction in the vascular permeability activity of BK when attached to the polymer carrier. P-BK pre-treatment improved blood flow in the tumor tissue by 1.4-1.7-fold, which was maintained for more than 4 h. In addition, P-BK pre-treatment increased the tumor accumulation of pegylated liposomal doxorubicin (PLD) by approximately 3-fold. Furthermore, P-BK pre-treatment led to superior antitumor activity of PLD and significantly improved the survival of tumor-bearing mice. The release of BK from P-BK in the acidic milieu of the tumor was a prerequisite for P-BK to exert its effect, as the vascular permeability enhancing activity of P-BK was negligible. Collectively, P-BK pre-treatment improved intratumoral blood flow and augmented tumor accumulation of nanomedicine, thereby resulting in a significant suppression of tumor growth. Therefore, these findings demonstrate that P-BK is a potential concomitant drug for improving the tumor delivery of nanomedicines.

• Klíčová slova
• Antitumor effect, Bradykinin, EPR effect, HPMA polymer, Nanomedicine,
• MeSH
• bradykinin terapeutické užití   MeSH
• doxorubicin terapeutické užití   MeSH
• methakryláty MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory * farmakoterapie   MeSH
• nanomedicína MeSH
• nosiče léků terapeutické užití   MeSH
• polymery terapeutické užití   MeSH
• protinádorové látky * terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bradykinin MeSH
• doxorubicin MeSH
• hydroxypropyl methacrylate MeSH Prohlížeč
• methakryláty MeSH
• nosiče léků MeSH
• polymery MeSH
• protinádorové látky * MeSH

B-cell non-Hodgkin lymphomas (B-NHL) represent the most common type of hematologic malignancies in the Western hemisphere. The therapy of all B-NHL is based on the combination of different genotoxic cytostatics and anti-CD20 monoclonal antibody (mAb) rituximab. Unfortunately, many patients relapse after the mentioned front-line treatment approaches. The therapy of patients with relapsed/refractory (R/R) B-NHL represents an unmet medical need. We designed, developed and tested novel actively targeted hybrid mAb-polymer-drug conjugate (APDC) containing anti-CD20, anti-CD38 or anti-CD19 mAbs. Biocompatible copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA) with cytostatic agent doxorubicin attached via stimuli-sensitive hydrazone bond were employed for the mAb grafting. Anti-lymphoma efficacy of the APDC nanotherapeutics was evaluated in vivo on a panel of three patient-derived lymphoma xenografts derived from two patients with R/R B-NHL and one patient with so far untreated B-NHL. In both PDX models derived from patients with R/R B-NHL, the targeting with anti-CD38 antibody daratumumab demonstrated highly improved anti-lymphoma efficacy compared to the targeting with anti-CD20 rituximab, two experimental anti-CD19 antibodies and non-targeted controls. The results represent a proof-of-concept of a new algorithm of personalized anti-tumor therapy based on highly innovative APDC biomaterials.

• Klíčová slova
• APDC, Active targeting, CD38, Daratumumab, Drug delivery, Non-Hodgkin lymphoma, Polymer nanomaterials, Rituximab,
• MeSH
• léčivé přípravky * MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nehodgkinský lymfom * farmakoterapie   MeSH
• polymery terapeutické užití   MeSH
• protinádorové látky * terapeutické užití   MeSH
• rituximab MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• daratumumab MeSH Prohlížeč
• léčivé přípravky * MeSH
• monoklonální protilátky MeSH
• polymery MeSH
• protinádorové látky * MeSH
• rituximab MeSH

OBJECTIVE: To evaluate the determinants of vaginal delivery and safety in women undergoing cervical ripening with a synthetic osmotic dilator (Dilapan-S) prior to induction of labor. METHODS: We conducted a secondary analysis of an international multicenter prospective observational study of Dilapan-S for cervical ripening in pregnancies greater than 32 weeks. Data were obtained in a standardized fashion and entered into a centralized electronic data capture system. The association between Bishop score and vaginal delivery was further evaluated with a multivariate receiver-operating characteristic (ROC) curve analysis. A Wilcoxon rank test and multivariable logistic regression were used for statistical analysis (significance: P < .05). RESULTS: Between May 2015 and July 2016, 444 pregnant women were included. Three hundred ten (70 %) delivered vaginally. Compared to patients who underwent cesarean delivery, those who delivered vaginally were more likely to have a history of prior vaginal delivery. Vaginal delivery rates were significantly correlated with Bishop scores of pre and post Dilapan-S and difference. After adjusting for age, BMI, number of dilators, cervical ripening time, and gestational age, both prior vaginal delivery and post-Dilapan-S Bishop scores were strong predictors of vaginal delivery (estimate coefficient: 0.1275 ± 0.03 P = .0002; 0.049 ± 0.01 P = .0001; respectively). Aggregate ROC accounting for these variables further supported these findings (AUC = 0.734). The lower confidence interval limit of vaginal delivery rates was above 50 % when post-Dilapan-S Bishop scores were ≥ 5. Cox regression analyses demonstrated that the duration of labor was significant shorter in women that had vaginal delivery. CONCLUSION: Bishop scores after cervical ripening with Dilapan-S are good predictors of vaginal delivery. Bishop scores < 5 post Dilapan-S may warrant further cervical ripening. Further level 1 trials are needed to compare osmotic dilators to other ripening methods.

• Klíčová slova
• Cervical ripening, Dilapan, Induction, Labor, Mechanical,
• MeSH
• časové faktory MeSH
• císařský řez statistika a číselné údaje   MeSH
• dospělí MeSH
• gestační stáří MeSH
• indukovaný porod metody   MeSH
• lidé MeSH
• mladý dospělý MeSH
• polymery terapeutické užití   MeSH
• proporcionální rizikové modely MeSH
• těhotenství MeSH
• vedení porodu statistika a číselné údaje   MeSH
• zrání děložního hrdla * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• dilapan MeSH Prohlížeč
• polymery MeSH

Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumor targeting ability. In this regard, nucleic acid-based drug (NABD) and particularly small interfering RNAs (siRNAs), are attractive molecules due to the possibility to be engineered to target specific tumor genes. On the other hand, polymeric-based delivery systems are emerging as versatile carriers to generate tumor-targeted delivery systems. Here we will focus on the most recent findings in the selection of siRNA/polymeric targeted delivery systems for hepatocellular carcinoma (HCC), a human tumor for which currently available therapeutic approaches are poorly effective. In addition, we will discuss the most attracting and, in our opinion, promising siRNA-polymer combinations for HCC in relation to the biological features of HCC tissue. Attention will be also put on the mathematical description of the mechanisms ruling siRNA-carrier delivery, this being an important aspect to improve effectiveness reducing the experimental work.

• Klíčová slova
• HCC, optimized drug delivery, siRNA,
• MeSH
• biologické modely * MeSH
• chemické modely MeSH
• hepatocelulární karcinom * farmakoterapie   genetika   metabolismus   patologie   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• malá interferující RNA * chemie   genetika   terapeutické užití   MeSH
• nádory jater * farmakoterapie   genetika   metabolismus   patologie   MeSH
• polymery * chemie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• malá interferující RNA * MeSH
• polymery * MeSH

New amphiphilic diblock polymer nanotherapeutics serving simultaneously as a drug delivery system and an inhibitor of multidrug resistance were designed, synthesized, and evaluated for their physico-chemical and biological characteristics. The amphiphilic character of the diblock polymer, containing a hydrophilic block based on the N-(2-hydroxypropyl)methacrylamide copolymer and a hydrophobic poly(propylene oxide) block (PPO), caused self-assembly into polymer micelles with an increased hydrodynamic radius (Rh of approximately 15nm) in aqueous solutions. Doxorubicin (Dox), as a cytostatic drug, was bound to the diblock polymer through a pH-sensitive hydrazone bond, enabling prolonged circulation in blood, the delivery of Dox into a solid tumor and the subsequent stimuli-sensitive controlled release within the tumor mass and tumor cells at a decreased pH. The applicability of micellar nanotherapeutics as drug carriers was confirmed by an in vivo evaluation using EL4 lymphoma-bearing C57BL/6 mice. We observed significantly higher accumulation of micellar conjugates in a solid tumor because of the EPR effect compared with similar polymer-drug conjugates that do not form micellar structures or with the parent free drug. In addition, highly increased anti-tumor efficacy of the micellar polymer nanotherapeutics, even at a sub-optimal dose, was observed. The presence of PPO in the structure of the diblock polymer ensured, during in vitro tests on human and mouse drug-sensitive and resistant cancer cell lines, the inhibition of P-glycoprotein, one of the most frequently expressed ATP-dependent efflux pump that causes multidrug resistance. In addition, we observed highly increased rate of the uptake of the diblock polymer nanotherapeutics within the cells. We suppose that combination of unique properties based on MDR inhibition, stimuli sensitiveness (pH sensitive activation of drug), improved pharmacokinetics and increased uptake into the cells made the described polymer micelle a good candidate for investigation as potential drug delivery system.

• Klíčová slova
• EPR effect, HPMA copolymer, Micellar drug conjugate, Multidrug resistance, P-glycoprotein inhibitor, Poly(propylene oxide),
• MeSH
• akrylamidy aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• chemorezistence účinky léků   MeSH
• doxorubicin aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lidé MeSH
• micely * MeSH
• mnohočetná léková rezistence účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• nosiče léků aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• polymery aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• propylenglykoly aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• protinádorová antibiotika aplikace a dávkování   chemie   farmakokinetika   terapeutické užití   MeSH
• tumor burden účinky léků   MeSH
• uvolňování léčiv MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• doxorubicin MeSH
• micely * MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• nosiče léků MeSH
• polymery MeSH
• polypropylene glycol MeSH Prohlížeč
• propylenglykoly MeSH
• protinádorová antibiotika MeSH

INTRODUCTION: Endovascular stent graft therapy of abdominal aortic aneurysms is sometimes complicated due to unusual anatomy of the aorta and adjacent arterial regions, an irregular or short proximal neck, numerous patent branches originating from the aneurysm, or tortuous iliac arteries. Endovascular aneurysm sealing is a new method designed to overcome certain limitations of current stent grafts. METHOD: At the Department of Vascular Surgery of Na Homolce Hospital, we implanted 51 stent grafts in the subrenal aorta and iliac arteries. Most of them were regular bifurcated stent grafts. Two patients were treated with the new Nellix stent graft, in one case due to a short subrenal neck of only 13 mm, and due to a considerably conical neck in the second case. RESULTS: The post-operative course was uneventful in both patients and they were discharged on the 5th postoperative day. CT angiography after six weeks proved that the stent graft had sealed well. The polymer filled the aortic lumen completely. CONCLUSION: This new method of endovascular aneurysm sealing (EVAS) of abdominal aortic aneurysm makes it possible to treat patients whose anatomy would normally require technically complex and more expensive endovascular methods. We aim to follow long-term results of the method in larger patient cohorts.

• MeSH
• aneurysma břišní aorty diagnostické zobrazování   chirurgie   MeSH
• aorta abdominalis chirurgie   MeSH
• aortografie MeSH
• arteria iliaca diagnostické zobrazování   chirurgie   MeSH
• cévní protézy MeSH
• cévy - implantace protéz metody   MeSH
• endovaskulární výkony metody   MeSH
• lidé MeSH
• počítačová rentgenová tomografie MeSH
• polymery terapeutické užití   MeSH
• stenty MeSH
• výkony cévní chirurgie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• polymery MeSH