Due to their large active surface, high loading efficiency, and tunable dissolution profiles, nanofibrous mats are often cited as promising drug carriers or antimicrobial membranes. Hyaluronic acid has outstanding biocompatibility, but it is hydrophilic. Nanofibrous structures made from hyaluronan dissolve immediately, making them unsuitable for controlled drug release and longer applications. We aimed to prepare a hyaluronan-based antimicrobial nanofibrous material, which would retain its integrity in aqueous environments. Self-supporting nanofibrous mats containing octenidine dihydrochloride or triclosan were produced by electrospinning from hydrophobized hyaluronan modified with a symmetric lauric acid anhydride. The nanofibrous mats required no cross-linking to be stable in PBS for 7 days. The encapsulation efficiency of antiseptics was nearly 100%. Minimal release of octenidine was observed, while up to 30% of triclosan was gradually released in 72 h. The nanofibrous materials exhibited antimicrobial activity, the fibroblast viability was directly dependent on the antiseptic content and its release.

• Klíčová slova
• Electrospinning, Lauroyl hyaluronan, Nanofiber, Octenidine, Triclosan,
• MeSH
• antibakteriální látky chemie   farmakologie   toxicita   MeSH
• buňky 3T3 MeSH
• hydrofobní a hydrofilní interakce MeSH
• iminy chemie   farmakologie   toxicita   MeSH
• kyselina hyaluronová chemie   farmakologie   toxicita   MeSH
• léky s prodlouženým účinkem chemie   farmakologie   toxicita   MeSH
• mikrobiální testy citlivosti MeSH
• myši MeSH
• nanovlákna chemie   toxicita   MeSH
• nosiče léků chemie   farmakologie   toxicita   MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• pyridiny chemie   farmakologie   toxicita   MeSH
• Staphylococcus aureus účinky léků   MeSH
• triclosan chemie   farmakologie   toxicita   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• iminy MeSH
• kyselina hyaluronová MeSH
• léky s prodlouženým účinkem MeSH
• nosiče léků MeSH
• octenidine MeSH Prohlížeč
• pyridiny MeSH
• triclosan MeSH

Solubilized dialdehyde cellulose (DAC), an efficient crosslinking agent for poly(vinyl alcohol) (PVA), provides less toxic alternative to current synthetic crosslinking agents such as glutaraldehyde, while simultaneously allowing for the preparation of hydrogels with comparably better characteristics. PVA/DAC hydrogels prepared using 0.5, 1 and 1.5 wt% of DAC were analyzed in terms of mechanical, swelling and cytotoxicity characteristics. Materials properties of PVA/DAC hydrogels range from stiff substances to soft viscoelastic gels capable of holding large amounts of water. Superior mechanical properties, porosity and surface area in comparison with analogical PVA/glutaraldehyde hydrogels were observed. Biological studies showed low toxicity and good biocompatibility of PVA/DAC hydrogels. Potential of PVA/DAC in mesh-controlled release of biologically active compounds was investigated using ibuprofen, rutin and phenanthriplatin. Hydrogel loaded with anticancer drug phenantriplatin was found effective against alveolar cancer cell line A549 under in vitro conditions.

• Klíčová slova
• Biomaterials, Crosslinking, Dialdehyde cellulose, Drug release, Hydrogel, Poly(vinyl alcohol),
• MeSH
• biokompatibilní materiály chemie   toxicita   MeSH
• celulosa analogy a deriváty   chemie   toxicita   MeSH
• fenantridiny chemie   MeSH
• hydrogely chemie   toxicita   MeSH
• ibuprofen chemie   MeSH
• lidé MeSH
• modul pružnosti MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků chemie   toxicita   MeSH
• organoplatinové sloučeniny chemie   MeSH
• polyvinylalkohol chemie   toxicita   MeSH
• reagencia zkříženě vázaná chemie   toxicita   MeSH
• rutin chemie   MeSH
• uvolňování léčiv MeSH
• viskoelastické látky chemie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2,3-dialdehydocellulose MeSH Prohlížeč
• biokompatibilní materiály MeSH
• celulosa MeSH
• fenantridiny MeSH
• hydrogely MeSH
• ibuprofen MeSH
• nosiče léků MeSH
• organoplatinové sloučeniny MeSH
• phenanthriplatin MeSH Prohlížeč
• polyvinylalkohol MeSH
• reagencia zkříženě vázaná MeSH
• rutin MeSH
• viskoelastické látky MeSH

The aim of the study was to prepare chemotherapeutic agent-loaded zinc oxide nanoparticles for the intracellular delivery of drug, for better therapeutic activity. Zinc oxide nanoparticles have inherent anticancer properties, hence it was envisaged that by loading the anticancer drug into zinc oxide nanoparticles, enhanced anticancer activity might be observed. Zinc oxide nanoparticles were prepared using zinc nitrate and sodium hydroxide. Starch was used as the stabilizing agent. The nanoparticles prepared were characterized for size, shape, entrapment efficiency, and drug release. Further, cell line studies were performed to evaluate cellular uptake and cytotoxicity profile using MCF-7 cells. A hemolysis study was performed to check the acute toxicity of the nanoparticles. The nanoparticles were found to be 476.4 ± 2.51 nm in size, with low PDI (0.312 ± 0.02) and high entrapment efficiency (> 85%). The nanoparticles were stable, and did not form aggregates on storage in the dispersed form. A cytotoxicity study demonstrated that drug-loaded zinc oxide nanoparticles exhibited higher anticancer activity as compared to either blank zinc oxide nanoparticles and doxorubicin (DOX) alone, or their mixture. A hemolytic test revealed that the prepared zinc oxide nanoparticles caused negligible hemolysis. Thus, it can be concluded that zinc oxide nanoparticles loaded with DOX resulted in better uptake of the chemotherapeutic agent, and at the same time, showed low toxicity towards normal cells.

• Klíčová slova
• Zinc oxide, anticancer, doxorubicin, drug delivery, nanoparticles,
• MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• doxorubicin chemie   farmakologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nanočástice * MeSH
• nosiče léků chemie   toxicita   MeSH
• oxid zinečnatý chemie   toxicita   MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• doxorubicin MeSH
• nosiče léků MeSH
• oxid zinečnatý MeSH

Polymer drug carriers that are based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers have been widely used in the development and synthesis of high-molecular-weight (HMW) drug delivery systems for cancer therapy. In this study, we compared linear (Mw ~27kDa, Rh ~4nm) and non-degradable star (Mw ~250kDa, Rh ~13nm) HPMA copolymer conjugates bearing anthracycline antibiotic doxorubicin (DOX) bound via pH-sensitive hydrazone bond. We determined the in vitro and in vivo toxicity of both conjugates and their maximum tolerated dose (MTD). We also compared their anti-tumour activity in mouse B-cell leukaemia (BCL1) and a mouse T-cell lymphoma (EL4) model. We found that MTD was higher for the linear conjugate (85mgDOX/kg) and lower for the star conjugate (22.5mgDOX/kg). An evaluation of the intestinal barrier integrity using FITC-dextran as a gut permeability tracer proved that no pathology was caused by the MTD of either conjugate. However, free DOX showed some damage to the gut barrier. The therapy of BCL1 leukaemia by both of the polymeric conjugates using the MTD or its fraction (i.e., equitoxic dosage) showed better results in the case of the star conjugate. On the other hand, treatment of EL4 lymphoma seemed to be more efficient when the linear conjugate was used. We suppose that the anti-cancer treatment of solid tumours and leukaemias requires different types of drug conjugates. We hypothesise that the most suitable HPMA copolymer-DOX conjugate for the treatment of solid tumours should have an HMW structure with increased Rh that would be stable for three to four days after the conjugate administration and then rapidly disintegrate in the short polymer chains, which are excretable from the body by glomerular filtration. On the other hand, the treatment of leukaemia requires a drug conjugate with a long circulation half-life. This would provide an active drug, whilst slowly degrading to excretable fragments.

• Klíčová slova
• Anti-tumour activity, Doxorubicin, HPMA, Structure, Toxicity,
• MeSH
• akrylamidy chemie   farmakokinetika   terapeutické užití   toxicita   MeSH
• antibiotika antitumorózní * chemie   farmakokinetika   terapeutické užití   toxicita   MeSH
• dendrimery chemie   farmakokinetika   terapeutické užití   toxicita   MeSH
• doxorubicin chemie   farmakokinetika   terapeutické užití   toxicita   MeSH
• játra účinky léků   patologie   MeSH
• kostní dřeň účinky léků   patologie   MeSH
• maximální tolerovaná dávka MeSH
• molekulová hmotnost MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory krev   farmakoterapie   metabolismus   MeSH
• nosiče léků * chemie   farmakokinetika   terapeutické užití   toxicita   MeSH
• slezina účinky léků   patologie   MeSH
• střevní sliznice metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• antibiotika antitumorózní * MeSH
• dendrimery MeSH
• doxorubicin MeSH
• N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate MeSH Prohlížeč
• nosiče léků * MeSH
• PAMAM Starburst MeSH Prohlížeč

Lyme disease caused by spirochete Borrelia burgdorferi sensu lato, is a tick-born illness. If the infection is not eliminated by the host immune system and/or antibiotics, it may further disseminate and cause severe chronic complications. The immune response to Borrelia is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies associated with Th1 cell activation. A new experimental vaccine was constructed using non-lipidized form of recombinant B. burgdorferi s.s. OspC protein was anchored by metallochelating bond onto the surface of nanoliposomes containing novel nonpyrogenic lipophilized norAbuMDP analogues denoted MT05 and MT06. After i.d. immunization, the experimental vaccines surpassed Alum with respect to OspC-specific titers of IgG2a, IgG2b isotypes when MT06 was used and IgG3, IgM isotypes when MT05 was used. Both adjuvants exerted a high adjuvant effect comparable or better than MDP and proved themselves as nonpyrogenic.

• MeSH
• acetylmuramyl-alanyl-isoglutamin chemie   toxicita   MeSH
• antigeny bakteriální imunologie   MeSH
• Borrelia burgdorferi imunologie   MeSH
• chelátory chemie   toxicita   MeSH
• diferenciální skenovací kalorimetrie MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• ELISA MeSH
• liposomy MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nanočástice chemie   toxicita   MeSH
• nosiče léků chemie   toxicita   MeSH
• proteiny vnější bakteriální membrány imunologie   MeSH
• protilátky bakteriální krev   MeSH
• radiační rozptyl MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• světlo MeSH
• transmisní elektronová mikroskopie MeSH
• vakcína proti lymeské nemoci aplikace a dávkování   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• antigeny bakteriální MeSH
• chelátory MeSH
• liposomy MeSH
• nosiče léků MeSH
• OspC protein MeSH Prohlížeč
• proteiny vnější bakteriální membrány MeSH
• protilátky bakteriální MeSH
• vakcína proti lymeské nemoci MeSH

Earlier studies have described promising antitumor activity of a large-ring chelate complex [PtCl(2)(cis-1,4-DACH)] (DACH=diaminocyclohexane). Encouraging antitumor activity of this analogue of cisplatin prompted us to perform studies focused on the mechanistic basis of pharmacological effects of this complex. Four early steps in the mechanism of biological activity of cisplatin have been delineated: cell entry, reactions with sulfur-containing compounds, platinum-DNA binding along with processing platinated DNA by proteins (enzymes) and DNA repair. Here, we describe comparative experiments (involving also cisplatin) revealing: (i) improved cytotoxicity (3.4-5.4-fold) of [PtCl(2)(cis-1,4-DACH)] in human tumor ovarian cell lines; (ii) enhanced cellular uptake (approximately 1.5-fold) of [PtCl(2)(cis-1,4-DACH)]; (iii) somewhat enhanced rate of reactions of [PtCl(2)(cis-1,4-DACH)] with glutathione (approximately 1.5-fold), but a similar rate of reactions with metallothionenin-2; (iv) enhanced rate of DNA binding of [PtCl(2)(cis-1,4-DACH)] in cell-free media (approximately 2-fold); (v) similar sequence preference of DNA binding of [PtCl(2)(cis-1,4-DACH)] in cell-free media; (vi) identical DNA interstrand cross-linking efficiency (6%); (vii) similar bending (32 degrees) and enhanced local unwinding (approximately 1.5-fold) induced in DNA by the major 1,2-GG-intrastrand cross-link; (viii) markedly enhanced inhibiting effects of DNA adducts of [PtCl(2)(cis-1,4-DACH)] on processivity of DNA polymerase; and (ix) a slightly lower efficiency of DNA repair systems to remove the adducts of [PtCl(2)(cis-1,4-DACH)] from DNA.

• MeSH
• antitumorózní látky chemie   metabolismus   farmakologie   MeSH
• buněčná membrána účinky léků   metabolismus   MeSH
• cyklohexylaminy chemie   metabolismus   farmakologie   MeSH
• DNA nádorová metabolismus   MeSH
• glutathion metabolismus   MeSH
• HeLa buňky MeSH
• králíci MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• nosiče léků chemie   metabolismus   toxicita   MeSH
• oprava DNA účinky léků   fyziologie   MeSH
• organoplatinové sloučeniny metabolismus   toxicita   MeSH
• skot MeSH
• sloučeniny platiny chemie   metabolismus   toxicita   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 1,4-diaminocyclohexane MeSH Prohlížeč
• antitumorózní látky MeSH
• cyklohexylaminy MeSH
• DNA nádorová MeSH
• glutathion MeSH
• ligandy MeSH
• nosiče léků MeSH
• organoplatinové sloučeniny MeSH
• platinum chloride MeSH Prohlížeč
• sloučeniny platiny MeSH

This study compares the toxic effects of native cyclosporia A (CyA) with those of targeted CyA that is conjugated with the anti-rat-thymocyte antibody of rabbit origin via the N-(2-hydroxypropyl)methacrylamide (HPMA) carrier bearing digestible, reactive oligopeptide side chains. Ten toxic doses of native CyA (50 mg/kg i.p.) given to young adult rats in the course of 14 d produced a severe renal lesion-diffuse microvacuolization of the proximal tubules in the deep cortex, and hypergranulation of juxtaglomerular regions. Severe atrophy of the thymic medulla was documented by morphometry. In the cortex the epithelial reticular (but not deep interdigitating) cells showed ultrastructural signs of severe degeneration and lysis. The immature CD4+8+ double-positive cortical lymphocytes were preserved whereas the single-positive medullary thymocytes were greatly depleted; there was also a restriction of MHC class II antigen expression in the medulla. The number of medullary B cells was increased. The cytokeratin net was focally shrunken in the cortex and almost negative in the medulla, with loss of Hassall's corpuscles. After ten corresponding doses of antibody-targeted conjugated CyA no damage to the renal tubules and arterioles appeared and the antiGBM or immune-complex deposition was absent. The thymus had a normal medulla with numerous mature thymocytes and the cortical epithelial reticulum remained well preserved. Thus, the main toxic effects of CyA could be eliminated by targeting. The T-cell-targeted drug was tested for preserved immunosuppressive properties and non-toxic character of HPMA copolymer carrier.

• MeSH
• cyklosporin toxicita   MeSH
• cyklosporiny toxicita   MeSH
• imunokonjugáty toxicita   MeSH
• imunosupresiva toxicita   MeSH
• krysa rodu Rattus MeSH
• ledviny účinky léků   MeSH
• nosiče léků toxicita   MeSH
• potkani Wistar MeSH
• T-lymfocyty účinky léků   imunologie   MeSH
• thymus účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cyklosporin MeSH
• cyklosporiny MeSH
• imunokonjugáty MeSH
• imunosupresiva MeSH
• nosiče léků MeSH