Burst drug release is often considered a negative phenomenon resulting in unexpected toxicity or tissue irritation. Optimal release of a highly soluble active pharmaceutical ingredient (API) from hypromellose (HPMC) matrices is technologically impossible; therefore, a combination of polymers is required for burst effect reduction. Promising variant could be seen in combination of HPMC and insoluble Eudragits® as water dispersions. These can be applied only on API/insoluble filler mixture as over-wetting prevention. The main hurdle is a limited water absorption capacity (WAC) of filler. Therefore, the object of this study was to investigate the dissolution behavior of levetiracetam from HPMC/Eudragit®NE matrices using magnesium aluminometasilicate (Neusilin® US2) as filler with excellent WAC. Part of this study was also to assess influence of thermal treatment on quality parameters of matrices. The use of Neusilin® allowed the application of Eudragit® dispersion to API/Neusilin® mixture in one step during high-shear wet granulation. HPMC was added extragranularly. Obtained matrices were investigated for qualitative characteristics, NMR solid-state spectroscopy (ssNMR), gel layer dynamic parameters, SEM, and principal component analysis (PCA). Decrease in burst effect (max. of 33.6%) and dissolution rate, increase in fitting to zero-order kinetics, and paradoxical reduction in gel layer thickness were observed with rising Eudragit® NE concentration. The explanation was done by ssNMR, which clearly showed a significant reduction of the API particle size (150-500 nm) in granules as effect of surfactant present in dispersion in dependence on Eudragit®NE amount. This change in API particle size resulted in a significantly larger interface between these two entities. Based on ANOVA and PCA, thermal treatment was not revealed as a useful procedure for this system.

• Klíčová slova
• Burst effect, Eudragit® NE30D, HPMC, Levetiracetam, Neusilin® US2, gel layer, matrix tablets, multivariate data analysis, thermal treatment,
• MeSH
• aplikace orální MeSH
• gely MeSH
• kyseliny polymethakrylové aplikace a dávkování   chemie   metabolismus   MeSH
• léky s prodlouženým účinkem aplikace a dávkování   chemie   metabolismus   MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• pomocné látky chemie   MeSH
• rozpustnost MeSH
• silikáty aplikace a dávkování   chemie   metabolismus   MeSH
• sloučeniny hliníku aplikace a dávkování   chemie   metabolismus   MeSH
• sloučeniny hořčíku aplikace a dávkování   chemie   metabolismus   MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aluminum magnesium silicate MeSH Prohlížeč
• gely MeSH
• kyseliny polymethakrylové MeSH
• léky s prodlouženým účinkem MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• pomocné látky MeSH
• silikáty MeSH
• sloučeniny hliníku MeSH
• sloučeniny hořčíku MeSH

Nanomedicines have provided fresh impetus in the fight against cancer due to their selectivity and power. However, these agents are limited when delivered intravenously due to their rapid clearance from the bloodstream and poor passage from the bloodstream into target tumours. Here we describe a novel stealthing strategy which addresses both these limitations and thereby demonstrate that both the passive and mechanically-mediated tumour accumulation of the model nanomedicine adenovirus (Ad) can be substantially enhanced. In our strategy gold nanoparticles were thoroughly modified with 2kDa polyethyleneglycol (PEG) and then linked to Ad via a single reduction-cleavable 5kDa PEG. The resulting Ad-gold-PEG construct was compared to non-modified Ad or conventionally stealthed Ad-poly[N-(2-hydroxypropyl)methacrylamide] (Ad-PHPMA). Notably, although Ad-gold-PEG was of similar size and surface charge to Ad-PHPMA the increase in density, resulting from the inclusion of the gold nanoparticles, provided a substantial enhancement of ultrasound-mediated transport. In an in vitro tumour mimicking phantom, the level and distance of Ad-gold-PEG transport was shown to be substantially greater than achieved with Ad-PHPMA. In in vivo studies 0.1% of an unmodified Ad dose was shown to accumulate in tumours, whereas over 12% of the injected dose was recovered from the tumours of mice treated with Ad-gold-PEG and ultrasound. Ultimately, a significant increase in anti-tumour efficacy resulted from this strategy. This stealthing and density-increasing technology could ultimately enhance clinical utility of intravenously delivered nanoscale medicines including viruses, liposomes and antibodies.

• Klíčová slova
• Delivery, Density, Pharmacokinetics, Stealthing, Tumour, Ultrasound, Virotherapy,
• MeSH
• Adenoviridae genetika   MeSH
• játra metabolismus   MeSH
• kovové nanočástice * aplikace a dávkování   chemie   MeSH
• kyseliny polymethakrylové aplikace a dávkování   chemie   MeSH
• lidé MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• nádorové buněčné linie MeSH
• nádory metabolismus   terapie   MeSH
• nanomedicína MeSH
• onkolytická viroterapie MeSH
• polyethylenglykoly * aplikace a dávkování   chemie   MeSH
• ultrazvuk MeSH
• zelené fluorescenční proteiny genetika   MeSH
• zlato * aplikace a dávkování   chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Duxon MeSH Prohlížeč
• kyseliny polymethakrylové MeSH
• polyethylenglykoly * MeSH
• zelené fluorescenční proteiny MeSH
• zlato * MeSH

Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor regression and to the development of therapy-dependent longlasting cancer resistance. This phenomenon occurs with two types of Dox conjugates tested, despite differences in the covalent linkage of Dox to the polymer carrier. Such a cancer resistance cannot fully express in conventional treatment with free Dox, due to substantial immunotoxicity of the treatment, which was not observed in the polymer conjugates. In this study, calreticulin (CRT) translocation and high mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox bound via an amide bond only increased translocation of HSPs to the membrane, which led to an elevated phagocytosis but was not sufficient to induce increase of the maturation markers on DCs in vitro. Both types of conjugates induced engulfment of the target tumor cells in vivo, that was more intense than that seen with free Dox. It means that the induction of anti-tumor immunity documented upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely solely on CRT-mediated cell death, but involves multiple mechanisms.

• MeSH
• antigeny CD80 metabolismus   MeSH
• antigeny CD86 metabolismus   MeSH
• apoptóza účinky léků   MeSH
• chemorezistence účinky léků   MeSH
• dendritické buňky cytologie   imunologie   MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   chemie   toxicita   MeSH
• fagocytóza MeSH
• kalretikulin metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny polymethakrylové aplikace a dávkování   chemie   toxicita   MeSH
• lymfom T-buněčný farmakoterapie   imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků chemie   MeSH
• protein HMGB1 metabolismus   MeSH
• proteiny teplotního šoku metabolismus   MeSH
• protinádorové látky aplikace a dávkování   chemie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD80 MeSH
• antigeny CD86 MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• kalretikulin MeSH
• kyseliny polymethakrylové MeSH
• nosiče léků MeSH
• protein HMGB1 MeSH
• proteiny teplotního šoku MeSH
• protinádorové látky MeSH

We have investigated the effects of low-frequency pulsed electromagnetic field (LF-EMF) produced by BEMER device on experimental mouse T-cell lymphoma EL4 growing on conventional and/or athymic (nude) mice. Exposure to EMF-BEMER slowed down the growth of tumor mass and prolonged the survival of experimental animals. The effect was more pronounced in immuno-compromised nude mice compared to conventional ones. Acceleration of tumor growth was never observed. No measurable levels of Hsp 70 or increased levels of specific anti-EL4 antibodies were detected in the serum taken from experimental mice before and at different intervals during the experiment, i.e. before solid tumor appeared, at the time of its aggressive growth, and at the terminal stage of the disease. A significant synergizing antitumor effect was seen when EL4 tumor-bearing mice were simultaneously exposed to EMF-BEMER and treated with suboptimal dose of synthetic HPMA copolymer-based doxorubicin, DOX(HYD)-HPMA. Such a combination may be especially useful for heavily treated patients suffering from advanced tumor and requiring additional aggressive chemotherapy which, however, at that time could represent almost life-threatening way of medication.

• MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   farmakologie   MeSH
• elektromagnetická pole * MeSH
• imunokompromitovaný pacient MeSH
• kombinovaná terapie MeSH
• kyseliny polymethakrylové aplikace a dávkování   farmakologie   MeSH
• lymfom T-buněčný patologie   terapie   MeSH
• míra přežití MeSH
• myši inbrední C57BL MeSH
• myši nahé MeSH
• myši MeSH
• proteiny tepelného šoku HSP70 metabolismus   MeSH
• protinádorová antibiotika aplikace a dávkování   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• kyseliny polymethakrylové MeSH
• proteiny tepelného šoku HSP70 MeSH
• protinádorová antibiotika MeSH

Coated hard capsules are becoming increasingly important for a number of reasons such as administration of new active ingredients, oral vaccination, colon drug delivery or their use in preclinical and clinical trials. The independency of coating composition on capsules filling is the major advantage of this dosage form. In our study, two types of hard capsules (gelatin and hypromellose) were coated by non-aqueous solutions of Eudragit L and S 12.5, respectively, to achieve intestinal and distal ileic drug delivery. Gelatin hard capsules were coated with Eudragit film either directly or using hydroxypropyl cellulose sub-coating prior to the final coating. Hypromellose capsules were coated directly. Coated capsules were evaluated for coating thickness by optical microscope and for dissolution in different pH media. Gelatin capsules do not seem to be suitable for direct coating with Eudragit due to insufficient film adhesion to the smooth capsule surface and a brittleness of formed films. These problems can be solved by hydroxypropyl celullose interlayer application. Hypromellose hard capsules could be directly easily coated with both Eudragit solutions. Dissolution of caffeine from coated capsules showed the potency for enteric delivery in gelatin capsules with interlayer and Eudragit L film in 7.5 and 10.0% concentrations and in hypromellose capsules coated with EudragitL in 5-17.5% coating levels. Gelatine capsules with interlayer and 10% Eudragit S film and hypromellose capsules only with high coating level (20%) provided potential distal ileum targeting of incorporated drug. Eudragit S film sprayed onto hypromellose capsules surface was brittle especially in the junction zone between capsule cap and body. Better plasticity of Eudragit S coating could be probably achieved using a different plasticizer.

• MeSH
• ileum metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny polymethakrylové aplikace a dávkování   MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• rozpustnost MeSH
• tobolky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kyseliny polymethakrylové MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• tobolky * MeSH

This paper reviews an early clinical experience with anthracycline (epirubicin; Epi or doxorubicin; Dox) containing an N-(2-hydroyxypropyl)methacrylamide copolymer carrier targeted with autologous or commercial human immunoglobulin in six patients aged 28-55 suffering from therapy-resistant metastatic cancer. More than 100 biochemical, hematological and immunological parameters, including nine tumor markers, were tested in blood samples taken 24 h after the first and up to 10 months after the last application. The intravenous application proceeded without serious adverse or side effects and did not require hospitalization. Cardiotoxicity was not observed. Four of six monitored patients attained stabilization of disease (liver ultrasound scan and bone computer tomography) with a very good quality of life lasting from seven up to 18 months. Positive response to the treatment was, among others, evaluated as decreased CA 15-3 and CEA tumor markers. In three of five tested patients the serum level of C-reactive protein was temporarily increased 72 h after the treatment. A stable or elevated number of peripheral blood reticulocytes together with activation of natural killer (NK) cells and lymphokine-activated killer (LAK) cells supports the data previously obtained in experimental animals pointing to a dual role, i.e. the cytotoxic and immunomobilizing character of doxorubicin-HPMA conjugates.

• MeSH
• akrylamidy chemie   MeSH
• chemorezistence MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• epirubicin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• hemangiosarkom farmakoterapie   MeSH
• imunoglobulin G aplikace a dávkování   imunologie   MeSH
• imunologické faktory aplikace a dávkování   imunologie   MeSH
• intravenózní imunoglobuliny aplikace a dávkování   imunologie   MeSH
• kvalita života MeSH
• kyseliny polymethakrylové aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lékové transportní systémy MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádorové biomarkery krev   MeSH
• nádory prsu farmakoterapie   MeSH
• nosiče léků chemie   MeSH
• protinádorová antibiotika aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• epirubicin MeSH
• imunoglobulin G MeSH
• imunologické faktory MeSH
• intravenózní imunoglobuliny MeSH
• kyseliny polymethakrylové MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• nádorové biomarkery MeSH
• nosiče léků MeSH
• protinádorová antibiotika MeSH

Synthesis and preliminary anticancer activity of new star-shaped immunoglobulin-containing polymer-doxorubicin (DOX) conjugates were investigated. The polymer precursors used for the synthesis of immunoglobulin-polymer-drug conjugates are based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, the anticancer drug DOX is attached to the immunoglobulin-modified polymer via a pH-sensitive hydrazone linkage. Such polymer-DOX conjugates are stable in aqueous solution at pH 7.4 (pH of blood plasma) and the drug is released in mildly acid environment at pH 5-5.5 (pH in endosomes or lysosomes of target cells). Semitelechelic copolymer chains are linked to the immunoglobulin via one-point attachment to avoid branching of the conjugate observed in our earlier studied systems. The cytostatic activity of the conjugates tested on several cancer cell lines was similar to that of free DOX.HCl and correlated with the sensitivity of a particular cell line to DOX. The star-shaped conjugates containing immunoglobulin showed a significantly higher antitumor activity in vivo than immunoglobulin-free non-targeted polymer conjugates when tested in mice bearing EL4 T-cell lymphoma.

• MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   chemie   farmakologie   MeSH
• imunoglobuliny aplikace a dávkování   chemie   MeSH
• imunokonjugáty aplikace a dávkování   chemie   MeSH
• kyseliny polymethakrylové aplikace a dávkování   chemie   farmakologie   MeSH
• lidé MeSH
• lymfom T-buněčný farmakoterapie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků aplikace a dávkování   chemická syntéza   chemie   MeSH
• protinádorová antibiotika aplikace a dávkování   chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• imunoglobuliny MeSH
• imunokonjugáty MeSH
• kyseliny polymethakrylové MeSH
• nosiče léků MeSH
• protinádorová antibiotika MeSH

The paper is dealing with the synthesis and properties of new, nontargeted or antibody-targeted pH-sensitive polymer-doxorubicin (DOX) conjugates designed as anticancer drugs facilitating site-specific therapy. These conjugates are stable and inactive during transport in the body but activate inside target cells as a result of pH changes outside and inside the cells. Cytotoxicity of the conjugates depends on the detailed structure of the polymer and of the spacer between the drug and polymer carrier. In both protective and therapeutic regimes of drug administration, the in vivo antitumor activity of the pH-sensitive conjugates containing DOX was significantly enhanced (T-cell lymphoma EL 4, C57BL/16 mice) in comparison with the free DOX or classic PK1, the PHPMA-DOX conjugate clinically tested at present.

• MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   farmakokinetika   MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny polymethakrylové aplikace a dávkování   farmakokinetika   MeSH
• lidé MeSH
• lymfom T-buněčný farmakoterapie   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   metabolismus   MeSH
• polymery aplikace a dávkování   farmakokinetika   MeSH
• protinádorové látky aplikace a dávkování   farmakokinetika   MeSH
• xenogenní modely - testy protinádorové aktivity metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• kyseliny polymethakrylové MeSH
• polymery MeSH
• protinádorové látky MeSH

Recently hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for BS-RNase modification to prevent its degradation in bloodstream or fast elimination. Polymer-conjugated BS-RNase preparations proved to be cytotoxic after intravenous or intraperitoneal application, whereas native BS-RNase was ineffective. Here RNase A unimer was conjugated with two HPMA polymers (classic and star) and their antitumor effects both in vitro and in vivo were compared with those of BS-RNase polymers. Surprisingly, the antitumor effect of RNase A conjugates was also pronounced. The RNase A conjugates (classic and star) injected intravenously to mice bearing melanoma tumor caused a significant reduction in tumor volume following ten doses of 5 and 1 mg/kg, respectively. Despite the antitumor activity observed in vivo, the in vitro tested cytotoxic activity of RNase A did not differ from that caused by native RNase A while native BS-RNase (50 microg/ml) totally inhibited DNA synthesis in treated cells. The experiments with 125I-labeled preparations demonstrated concentration-dependent internalization of native BS-RNase by tumor cells within an hour, whereas the polymer conjugate (S-BS) was not internalized. On the contrary, the in vivo experiments showed that whereas 40% of S-BS conjugate persisted in bloodstream for 24h after administration, 98% of the native BS-RNase was already eliminated. Improved antitumor activities of PHPMA-modified RNases in vivo might be ascribed to their prolonged retention in bloodstream, better proteolytic stability and resistance to the action of the ribonuclease inhibitor.

• MeSH
• endoribonukleasy aplikace a dávkování   chemie   terapeutické užití   MeSH
• injekce intraperitoneální MeSH
• injekce intravenózní MeSH
• konformace proteinů MeSH
• kyseliny polymethakrylové aplikace a dávkování   chemie   MeSH
• lidé MeSH
• lymfocyty metabolismus   MeSH
• melanom experimentální farmakoterapie   patologie   MeSH
• molekulární struktura MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buňky kultivované metabolismus   MeSH
• nosiče léků MeSH
• pankreatická ribonukleasa aplikace a dávkování   chemie   terapeutické užití   MeSH
• protinádorové látky aplikace a dávkování   chemie   terapeutické užití   MeSH
• radioizotopy jodu MeSH
• skot MeSH
• vazebná místa fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• způsoby aplikace léků MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Duxon MeSH Prohlížeč
• endoribonukleasy MeSH
• kyseliny polymethakrylové MeSH
• nosiče léků MeSH
• pankreatická ribonukleasa MeSH
• protinádorové látky MeSH
• radioizotopy jodu MeSH
• ribonuclease SPL MeSH Prohlížeč

Binding of HPMA copolymer-conjugated doxorubicin targeted with monoclonal antibodies directed against various T-cell surface receptors, i.e. Thy1.2 (CDw90), I-A (MHC class II. glycoprotein), L3T4 (CD4), IL-2R (CD25) and CD3, is considerably increased in Con A stimulated T-lymphocytes. FACS analysis showed that the binding is most intensive with anti-Thy1.2 and anti-L3T4 targeted derivatives and it is proportional to the antiproliferative effect of the antibody-targeted drug. No binding and no antiproliferative capacity was observed after in vitro incubation of mouse T-cells with a nonspecific mouse IgG-HPMA-DOX conjugate. [3H]-TdR incorporation was inhibited considerably more in Con A stimulated T-cell culture and in EL4 mouse T-cell lymphoma as compared with the culture of nonactivated T-lymphocytes. This proves that intensively proliferating cells are more susceptible to the inhibitory action of an antibody-targeted drug. The cytotoxic efficacy of HPMA copolymer with GlyPheLeuGly or GlyLeuPheGly side-chains to which the drug is conjugated was superior to HPMA copolymer with GlyPheGly or GlyLeuGly side-chains. However, there is no direct correlation between the rate of in vitro drug release and the in vitro cytotoxicity of the respective conjugates. This suggests that the rate of drug release from the conjugate is only one factor responsible for the pharmacological efficacy of the preparation. Furthermore, we detected substantial and prolonged inhibition of proliferation of Con A activated T-cells only if doxorubicin was injected in vivo in the form of an anti-Thy1.2-targeted conjugate.

• MeSH
• aktivace lymfocytů MeSH
• antigeny povrchové imunologie   MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   MeSH
• konkanavalin A MeSH
• krysa rodu Rattus MeSH
• kyseliny polymethakrylové aplikace a dávkování   MeSH
• lidé MeSH
• monoklonální protilátky imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nosiče léků MeSH
• radioizotopy jodu MeSH
• sekvence aminokyselin MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny povrchové MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• konkanavalin A MeSH
• kyseliny polymethakrylové MeSH
• monoklonální protilátky MeSH
• nosiče léků MeSH
• radioizotopy jodu MeSH