- Klíčová slova
- magnetické zlaté nanočástice,
- MeSH
- chitosan MeSH
- doxorubicin * MeSH
- lidé MeSH
- magnetické nanočástice * MeSH
- nádory prsu farmakoterapie MeSH
- nosiče léků chemická syntéza MeSH
- systémy cílené aplikace léků * MeSH
- zinek MeSH
- zlato MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Klíčová slova
- magnetické zlaté nanočástice,
- MeSH
- doxorubicin * MeSH
- fullereny * MeSH
- geny BRCA2 MeSH
- lidé MeSH
- magnetické nanočástice MeSH
- mutace MeSH
- nádory prsu farmakoterapie genetika MeSH
- nosiče léků * chemická syntéza MeSH
- oligodeoxyribonukleotidy MeSH
- protein BRCA2 genetika MeSH
- zlato MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
In this study, we compared the enhanced permeability and retention (EPR) effect, toxicity, and therapeutic effect of the conjugate of the linear polymer poly(N-(2-hydroxypropyl)methacrylamide) (HPMA) with pirarubicin with an Mw below the renal threshold (39g/mol) (named LINEAR) and the disulfide-linked tandem-polymeric dimer of the poly(HPMA)-pirarubicin conjugate with an Mw above the renal threshold (93g/mol) (named DIBLOCK). The DIBLOCK conjugate, which was susceptible to reductive degradation, showed both a better EPR effect (tumor delivery) (2.5 times greater at 24h) and a prolonged plasma half-life. In addition, DIBLOCK had a better antitumor effect, as judged by percent survival, than did LINEAR (80% vs 65% at 150days), without any apparent toxicity in an S180 tumor model. However, the LD50 value of LINEAR was slightly higher than that of DIBLOCK (50mg/kg vs 37.5mg/kg, respectively). DIBLOCK required a longer time than LINEAR to reach maximum accumulation in the tumor. DIBLOCK also showed a greater time-dependent increase in the concentration in the tumor compared with the plasma concentration.
- MeSH
- antitumorózní látky škodlivé účinky chemie farmakologie MeSH
- biologická dostupnost MeSH
- biologický transport MeSH
- doxorubicin škodlivé účinky analogy a deriváty chemie farmakologie MeSH
- kyseliny polymethakrylové chemická syntéza MeSH
- lidé MeSH
- molekulová hmotnost MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemická syntéza MeSH
- poločas MeSH
- renální reabsorpce MeSH
- tkáňová distribuce MeSH
- uvolňování léčiv MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Sponge-type nanocarriers (spongosomes) are produced upon dispersion of a liquid crystalline sponge phase formed by self-assembly of an amphiphilic lipid in excess aqueous phase. The inner organization of the spongosomes is built-up by randomly ordered bicontinuous lipid membranes and their surfaces are stabilized by alginate chains providing stealth properties and colloidal stability. The present study elaborates spongosomes for improved encapsulation of Brucea javanica oil (BJO), a traditional Chinese medicine that may strongly inhibit proliferation and metastasis of various cancers. The inner structural organization and the morphology characteristics of BJO-loaded nanocarriers at varying quantities of BJO were determined by cryogenic transmission electron microscopy (Cryo-TEM), small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Additionally, the drug loading and drug release profiles for BJO-loaded spongosome systems also were determined. We found that the sponge-type liquid crystalline lipid membrane organization provides encapsulation efficiency rate of BJO as high as 90%. In vitro cytotoxicity and apoptosis study of BJO spongosome nanoparticles with A549 cells demonstrated enhanced anti-tumor efficiency. These results suggest potential clinical applications of the obtained safe spongosome formulations.
- MeSH
- antitumorózní látky fytogenní aplikace a dávkování chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- Brucea chemie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nanočástice chemie MeSH
- nosiče léků chemická syntéza chemie MeSH
- oleje aplikace a dávkování chemie farmakologie MeSH
- povrchové vlastnosti MeSH
- proliferace buněk účinky léků MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the presented research was to formulate, prepare and evaluate novel film wound dressings containing lidocaine hydrochloride. The conversion of partially substituted fibrous sodium carboxymethylcellulose (CMC) to an acidic form of CMC enabled the formation of an insoluble matrix which consequently provided the prepared films with excellent handling properties in their wet state. The drug concentration which was incorporated into an external layer of the film was 5 mg/cm2. The films demonstrated satisfactory mass and drug content uniformity as well as an acidic surface pH advantageous for wound application. An in vitro drug release test proved that the insoluble CMC matrix served as a reliable carrier without slowing down the release of lidocaine hydrochloride − more than 90% of the drug was released during the first 15 min, indicating a quick rate of anesthetic action. The prepared films could be potential wound dressings for comfortable and efficient topical anesthesia before/after procedures on the wound.
- MeSH
- anestetika lokální * MeSH
- bolest farmakoterapie MeSH
- chemie farmaceutická MeSH
- lékové formy MeSH
- lidokain MeSH
- lokální anestezie MeSH
- nosiče léků chemická syntéza chemie MeSH
- obvazy * MeSH
- povrchové vlastnosti MeSH
- rány a poranění terapie MeSH
- sodná sůl karboxymethylcelulosy * chemie MeSH
- systémy cílené aplikace léků MeSH
- techniky in vitro MeSH
- uvolňování léčiv MeSH
- Publikační typ
- práce podpořená grantem MeSH
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7.4) and hydrolytically degradable in mildly acidic environments (e.g. in endosomes or lysosomes, pH~5.0-6.5). Polymer-AtrHy conjugates were designed to achieve prolonged blood circulation and release of the immunomodulator intracellularly or extracellularly in solid tumor tissue. Three types of polymer precursors, differing in the structure of the keto acid-containing side chains, were synthesized. A linkage susceptible to hydrolytic cleavage was formed by the conjugation reaction of the carbonyl group-terminated side chains of the polymer precursors with the hydrazide group of a drug derivative. In vitro incubation of the conjugates in buffers resulted in much faster release of the drugs or their derivatives from the polymer at pH 5.0 than at pH 7.4, with the rate depending on the detailed structure of the spacer. Both the AtrHy derivative and its polymer conjugates showed the ability to induce the differentiation of retinoid-responsive HL-60 cells, thus demonstrating the required biological activity.
- MeSH
- antitumorózní látky farmakokinetika MeSH
- HL-60 buňky MeSH
- lidé MeSH
- methakryláty chemie MeSH
- nosiče léků chemická syntéza MeSH
- tretinoin farmakokinetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cytarabine is one of the most efficient drugs in the treatment of hematological malignancies. In this work, we describe the synthesis and characterization of two different polymer conjugates of cytarabine that were designed for the controlled release of cytarabine within the leukemia cells. Reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 3-(3-methacrylamidopropa-noyl)thiazolidine-2-thione) or 3-(Nmethacryloylglycyl-phenylalanylleucylglycyl)thiazolidine-2-thione were used in the study as reactive polymer precursors for reaction with cytarabine. The enzymatic release of cytarabine from the conjugate containing a GFLG spacer utilizing cathepsin B was verified. In addition to enzymolysis, the pH-dependent hydrolysis of cytarabine from both copolymers was also confirmed. Approximately 40 % and 20 % of the drug was released by spontaneous hydrolysis at pH 7.4 within 72 h from the polymer conjugates with the GFLG and beta-Ala spacers, respectively. At pH 6.0, the spontaneous hydrolysis slowed down, and less than 10 % of the drug was liberated within 72 h. The results of the cytotoxicity evaluation of the polymer conjugates in vitro against various cell lines showed that the cytotoxicity of the polymer conjugates is approximately three times lower in comparison to free cytarabine.
In this work, the encapsulation of cytotoxic drug doxorubicin (DOX) in protein nanocarrier apoferritin was studied. Two encapsulation protocols, using the disassembly and reassembly of apoferritin molecules in different surrounding pH and infusion method of encapsulation, were compared. The changes in size distribution and zeta potential of apoferritin in dependence to the pH changes, doxorubicin encapsulation and apoferritin:doxorubicin number of molecules ratio (1:14; 1:28; 1:56) were observed. The encapsulation efficiency at 1:56 apoferritin:doxorubicin ratio was 70% via pH changing method and 88% via infusion method. The release of doxorubicin molecules from nanocarrier after 14 days of storage at -20; 4; 20 and 37 °C was studied using capillary electrophoresis with laser induced fluorescence detection. The most stable was the storage at -20 ° with the infusion encapsulation method (after 14 days 0.32% DOX release). Due to very low release of cytotoxic drug molecules from apoferritin, apoferritin seems to be a suitable nanocarrier. Based on the size distribution changes, encapsulation efficiency and doxorubicin release, the infusion encapsulation method seems more promising.
- Klíčová slova
- enkapsulace, laser induced fluorescence,
- MeSH
- apoferritiny * MeSH
- časové faktory MeSH
- doxorubicin * MeSH
- elektroforéza kapilární MeSH
- fluorescence MeSH
- koncentrace vodíkových iontů MeSH
- nanomedicína MeSH
- nosiče léků * chemická syntéza MeSH
- velikost částic MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
This study describes a one-pot synthesis of superparamagnetic maghemite-based 4-aminobenzoic acid-coated spherical core-shell nanoparticles (PABA@FeNPs) as suitable nanocomposites potentially usable as magnetic carriers for drug delivery. The PABA@FeNPs system was subsequently functionalized by the activated species (1* and 2*) of highly in vitro cytotoxic cis-[PtCl2(3Claza)2] (1; 3Claza stands for 3-chloro-7-azaindole) or cis-[PtCl2(5Braza)2] (2; 5Braza stands for 5-bromo-7-azaindole), which were prepared by a silver(I) ion assisted dechlorination of the parent dichlorido complexes. The products 1*@PABA@FeNPs and 2*@PABA@FeNPs, as well as an intermediate PABA@FeNPs, were characterized by a combination of various techniques, such as Mössbauer, FTIR and EDS spectroscopy, thermal analysis, SEM and TEM. The results showed that the products consist of well-dispersed maghemite-based nanoparticles of 13 nm average size that represent an easily obtainable system for delivery of highly cytotoxic cisplatin-like complexes in oncological practice.
- MeSH
- antitumorózní látky chemie MeSH
- cisplatina aplikace a dávkování chemie MeSH
- indoly chemická syntéza chemie MeSH
- kyselina 4-aminobenzoová aplikace a dávkování chemická syntéza chemie MeSH
- lidé MeSH
- nádory farmakoterapie MeSH
- nanočástice chemie MeSH
- nosiče léků chemická syntéza chemie MeSH
- stříbro chemie MeSH
- systémy cílené aplikace léků * MeSH
- železité sloučeniny chemická syntéza chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The synthesis, characterization and results of evaluation of the biological behavior of HPMA copolymer conjugates bearing anti-cancer drugs doxorubicin and mitomycin C are described. Two HPMA copolymer carrier types were synthesized: the linear copolymer and the biodegradable high-molecular-weight diblock copolymer containing a degradable disulfide bond. The polymer-drug conjugates incubated in buffers modeling the intracellular environment released the drugs more rapidly than those incubated in bloodstream conditions. Significant in vitro and in vivo antitumor synergistic activity of the conjugates in the treatment of EL-4 T-cell demonstrates their high potential for solid tumor treatment.
- MeSH
- akrylamidy chemie MeSH
- analýza přežití MeSH
- antitumorózní látky chemie farmakologie MeSH
- B-buněčný lymfom farmakoterapie mortalita patologie MeSH
- cytotoxiny chemie farmakologie MeSH
- disulfidy MeSH
- doxorubicin chemie farmakologie MeSH
- karcinom plic Lewisové farmakoterapie mortalita patologie MeSH
- karcinom farmakoterapie mortalita patologie MeSH
- kinetika MeSH
- kombinovaná farmakoterapie MeSH
- kyseliny levulové chemie MeSH
- lymfom T-buněčný farmakoterapie mortalita patologie MeSH
- mitomycin chemie farmakologie MeSH
- mléčné žlázy zvířat účinky léků patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemická syntéza MeSH
- transplantace nádorů MeSH
- tumor burden účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH