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At least 91 records · Page 5Linked to original sources
PubMed2006

Poly-alpha,beta-(N-(2-hydroxyethyl)-L-aspartamide)-g-poly(1,3trimethylene carbonate) amphiphilic graft co-polymer as a potential drug carrier.

A biodegradable amphiphilic graft polymer was successfully synthesized by grafting hydrophobic poly(1,3-trimethylene carbonate) (PTMC) sequences onto a hydrophilic poly-alpha,beta-(N-(2-hydroxyethyl)-L-aspartamide) (PHEA) backbone. The graft polymer, PHEA-g-PTMC, was synthesized by ring-opening polymerization initiated by the macroinitiator PHEA bearing hydroxyl groups without adding any catalyst. The graft polymer was characterized by Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance spectroscopy, combined size-exclusion chromatography and multiangle laser light scattering analysis. Two drugs with distinct water solubility, prednisone acetate and tegafur, were encapsulated in the PHEA-g-PTMC nanoparticles. The in vitro release of two drugs from PHEA-g-PTMC nanoparticle drug-delivery systems was investigated.

Biocompatible Materials↗
PubMedDate not supplied

PEG-g-poly(GdDTPA-co-L-cystine): effect of PEG chain length on in vivo contrast enhancement in MRI.

Biodegradable macromolecular Gd(III) complexes, Gd-DTPA cystine copolymers (GDCP), were grafted with PEG of different sizes to modify the physicochemical properties and in vivo MRI contrast enhancement of the agents and to study the effect of PEG chain length on these properties. Three new PEG-grafted biodegradable macromolecular gadolinium(III) complexes were synthesized and characterized as blood pool MRI contrast agents. One of three different lengths of MPEG-NH(2) (MW = 550, 1000, and 2000) was grafted to the backbone of GDCP to yield PEG(n)()-g-poly(GdDTPA-co-l-cystine), PEG(n)()-GDCP. The PEG chain length did not dramatically alter the T(1) relaxivity, r(1), of the modified agents. The MRI enhancement profile of PEG(n)()-GDCP with different PEG sizes was significantly different in mice with respect to both signal intensity and clearance profiles. PEG(2000)-GDCP showed more prominent enhancement in the blood pool for a longer period of time than either PEG(1000)-GDCP or PEG(550)-GDCP. In the kidney, PEG(2000)-GDCP had less enhancement at 2 min than PEG(1000)-GDCP, but both PEG(550)-GDCP and PEG(1000)-GDCP showed a more pronounced signal decay thereafter. The three agents behaved similarly in the liver, as compared to that in the heart. All three agents showed little enhancement in the muscle. Chemical grafting with PEG of different chain lengths is an effective approach to modify the physiochemistry and in vivo contrast enhancement dynamics of the biodegradable macromolecular contrast agents. The novel agents are promising for further clinical development for cardiovascular and cancer MR imaging.

Animals↗
PubMedDate not supplied

[Combined antiviral effect of synthetic polyribonucleotide interferonogens and specific antiviral antibodies in arbovirus infections].

A model of tick-borne encephalitis in BALB/c mice was used to investigate the protective anti-viral effect of an interferon inducer, poly(G).poly(C), and specific gamma-globulin administered to the animals together or separately in small doses 24 hours before or after virus inoculation. Administration to the animals of poly(G).poly(C) alone or gamma-globulin alone was shown to produce a poor protective effect. Simultaneous administration of both preparations resulted in a significant decrease of mouse mortality after infection. As a result of the pretreatment of chick embryo cell cultures with poly(G).poly(C) before inoculation and the addition of specific immune serum to the agar overlay after the Sindbis virus inoculation, its multiplication was inhibited much more than after treatment of the cells with interferon inducer alone or antibody alone. Possible mechanisms of the observed additive antiviral effects of the interferon inducer and antibody, including those associated with the influence on the virus-induced interferon production, as well as the possibility of their combined use for the prevention and treatment of viral infections are discussed.

Animals↗
PubMed2006

Synthesis and characterization of poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(L-lactide) biodegradable copolymers as drug carriers.

A series of biodegradable amphiphilic graft polymers were successfully synthesized by grafting poly(L-lactide) (PLLA) sequences onto a water-soluble polymer poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. We established the feasibility of preparing these novel graft polymers by the ring-opening polymerization initiated by the macroinitiator PHEA bearing hydroxyl groups without adding any catalyst. The successful grafting of PLLA sequences onto the PHEA backbone was verified by combined size exclusion chromatography (SEC) and multiangle laser light scattering (MALLS) analysis. The chemical structures of graft polymers were characterized by FTIR and (1)H NMR. The critical micelle concentration (CMC) of the graft polymer was determined by fluorescence probe technique using pyrene. By controlling the feed ratio of the macroinitiator to the monomer, graft polymers with different branch lengths can be obtained. Using the 3-(4,5 dimethylthiozol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, the graft copolymer has been proved to have low cytotoxicity. Based on the amphiphilicity of the graft copolymers, nanoparticular drug delivery systems were prepared by the direct dissolution method and the dialysis method. The anticancer drug Tegafur was encapsulated into polymeric nanoparticles, and in vitro drug release behavior was investigated. Transmission electron microscopy (TEM) images demonstrate that these nanoparticles are regularly spherical in shape. The particle size and distribution of the nanoparticles were measured.

Animals↗
PubMedDate not supplied

Synthesis, characterization, and degradation behavior of amphiphilic poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(epsilon-caprolactone).

A series of biodegradable amphiphilic graft polymers were successfully synthesized by grafting poly(epsilon-caprolactone) (PCL) sequences onto a water-soluble poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. The graft copolymers were prepared through the ring-opening polymerization of epsilon-caprolactone (CL) initiated by the macroinitiator PHEA with pendant hydroxyl groups without adding any catalyst. By controlling the feed ratio of the macroinitiator to the monomer, the copolymers with different branch lengths and properties can be obtained. The successful grafting of PCL sequences onto the PHEA backbone was verified by FTIR, 1H NMR, and combined size-exclusion chromatography and multiangle laser light scattering (SEC-MALLS) analysis. The hydrolytic degradation and enzymatic degradation of these graft copolymers were investigated. The results show the hydrolytic degradation rate increases with increasing content of hydrophilic PHEA backbone. While the enzymatic degradation rate is affected by two competitive factors, the catalytic effect of Pseudomonas cepacia lipase on the degradation of PCL branches and the hydrophilicity which depends on the copolymer composition. In situ observation of the degradation under polarizing light microscope (PLM) demonstrates the different degradation rates of different regions in the polymer samples.

Aspartic Acid↗
PubMed1987

Complexes of polyriboguanylate with modified polyribocytidylate.

It was established minimal length of continuous poly(C) sequence of poly(G).poly(C) complex required for effective interferon induction by investigation poly(G).poly(C,A) with different molar ratios of C:A varying from 10:1 to 90:1. The minimum length of the double-stranded sequence of the macromolecule complex poly(G).poly(C) is equal to at least 90-100 nucleotides. The effect of 5-halogen-polyribocytidilates on the properties of the complexes has been also investigated.

Adenosine Diphosphate↗
PubMed1978

[Antiviral activity of the complexes obtained at different ratios of complementary homopolyribonucleotides].

Antiviral activity of the complexes of synthetic polyribonucleotides, i.e. poly (I).poly (C) and poly (G).poly (C) obtained at non-equimolar ratios of homopolymers was studied. The system of chick embryon fibroblasts and horse Venezuellan eguine encephalitis virus served as the model. It was shown that the active and stable complexes poly (I).poly (C) and poly (G).poly (C) were formed at some excess of poly (C), i.e. at the ratio of poly G) or poly (I) to poly (C) equal to 40/60 to 20/80 molar per cent. The role of the excessive poly (C) in formation of the stable secondary structure of the nucleotide complexes and its significance as one of the means for affecting the fine structure of double-stranded RNA were discussed.

Animals↗
PubMedDate not supplied

[Hydrolysis and the inactivation of double-stranded polyribonucleotides by monkey blood serum].

The effect of Macaca rhesus monkey blood serum on double-stranded polyribonucleotide complexes poly (I).poly (C), poly (G).poly (C), and poly (G,I).poly (C) was studied. The poly (I).poly (C) complex was found to be the most sensitive to hydrolysis as indicated by a decrease of the molecular weight, accumulation of acid-soluble products and a sharp decline of the antiviral and interferon-inducing activities in tissue culture after incubation of the complex in the presence of the serum at 37 degrees C for 1 hour. The poly (G).poly (C) complex was the most stable, and retained its original activity in tissue culture and a high molecular weight after 3-hour incubation with the serum. The interferon-inducing activity of all the complexes under study assayed by intravenous injection in a dose of 2 mg to M. rhesus monkeys was similarly low irrespective of their sensitivity to the serum. Conjectural species features of the interferon induction system in monkeys are discussed.

Animals↗
PubMed1986

Stopped-flow kinetic analysis of the interaction of anthraquinone anticancer drugs with calf thymus DNA, poly[d(G-C)].poly[d(G-C)], and poly[d(A-T)].poly[d(A-T)].

The sodium dodecyl sulfate driven dissociation reactions of daunorubicin (1), mitoxantrone (2), ametantrone (3), and a related anthraquinone without hydroxyl groups on the ring or side chain (4) from calf thymus DNA, poly[d(G-C)]2, and poly[d(A-T)]2 have been investigated by stopped-flow kinetic methods. All four compounds exhibit biphasic dissociation reactions from their DNA complexes. Daunorubicin and mitoxantrone have similar dissociation rate constants that are lower than those for ametantrone and 4. The effect of temperature and ionic strength on both rate constants for each compound is similar. An analysis of the effects of salt on the two rate constants for daunorubicin and mitoxantrone suggests that both of these compounds bind to DNA through a mechanism that involves formation of an initial outside complex followed by intercalation. The daunorubicin dissociation results from both poly[d(G-C)]2 and poly[d(A-T)]2 can be fitted with a single exponential function, and the rate constants are quite close. The ametantrone and 4 polymer dissociation results can also be fitted with single exponential curves, but with these compounds the dissociation rate constants for the poly[d(G-C)]2 complexes are approximately 10 times lower than for the poly[d(A-T)]2 complexes. Mitoxantrone also has a much slower dissociation rate from poly[d(G-C)]2 than from poly[d(A-T)]2, but its dissociation from both polymers exhibits biphasic kinetics. Possible reasons for the biphasic behavior with the polymers, which is unique to mitoxantrone, are selective binding and dissociation from the alternating polymer intercalation sites and/or dual binding modes of the intercalator with both side chains in the same groove or with one side chain in each groove.

Anthraquinones↗
PubMed1978

Differential susceptibilities of DNA polymerases-alpha and -beta to polyanions.

The effects of various polyanions including synthetic polynucleotides on DNApolymerases-alpha and -beta from blastulae of the sea urchin Hemicentrotus pulcherrimus and HeLa cells were studied. Only DNA polymerase-alpha was inhibited by polyanions, such as polyvinyl sufate, dextran sulfate, heparin, poly(G), poly(I), poly(U) and poly(ADP-Rib). Of the various polynucleotides tested, poly(G) and poly(I) were the strongest inhibitors. Kinetic studies showed that the Ki value for poly(G) was 0.3 microgram/ml and that poly(G) had 20-fold higher affinity than activated DNA for the template-primer site of DNA polymerase-alpha. Poly(U) and poly(ADP-Rib) were also inhibitory, but they were one hundredth as inhibitory as poly(G) or poly(I). Poly(A), poly(C), poly(A).poly(U) AND POLY(I).poly(C) were not inhibitory to DNA polymerase-alpha. In contrast, DNA olymerase-beta was not affected at all by these polyanions under the same conditions.

Animals↗
PubMed2002

Photohydrolysis of methotrexate produces pteridine, which induces poly-G-specific DNA damage through photoinduced electron transfer.

Methotrexate (MTX), an antineoplastic agent, demonstrates phototoxicity. The mechanism of damage to biomacromolecules induced by photoirradiated MTX was examined using 32P-labeled DNA fragments obtained from a human gene. Photoirradiated MTX caused DNA cleavage specifically at the underlined G in 5'-GG and 5'-GGG sequences in double-stranded DNA only when the DNA fragments were treated with piperidine, which suggests that DNA cleavage was caused by base modification with little or no strand breakage. With denatured single-stranded DNA the damage occurred at most guanine residues. The amount of formation of 8-hydroxy-2'-deoxyguanosine (8-oxodGuo), an oxidative product of 2'-deoxyguanosine, in double-stranded DNA exceeded that in single-stranded DNA. These results suggest that photoirradiated MTX participates in 8-oxodGuo formation at the underlined G in 5'-GG and 5'-GGG sequences in double-stranded DNA through electron transfer, and then 8-oxodGuo undergoes further oxidation into piperidine-labile products. Fluorescence measurement, high-pressure liquid chromatography and mass spectrometry have demonstrated that photoexcited MTX is hydrolyzed into 2,4-diamino-6-(hydroxymethyl)pteridine (DHP). DNA damage induced by DHP was observed in a similar manner as was the damage induced by MTX. The extent of DNA damage and the formation of 8-oxodGuo by DHP were much larger than those induced by MTX. The kinetic analysis, based on the time course of DNA oxidation by photoirradiated MTX, suggests that DNA damage is caused by photoexcited DHP rather than by photoexcited MTX. In conclusion, photoexcited MTX undergoes hydrolysis through intramolecular electron transfer, resulting in the formation of DHP, which exhibits a phototoxic effect caused by oxidation of biomacromolecules through photoinduced electron transfer.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1985

Reversible helix/coil transitions of left-handed Z-DNA structures. Comparison of the thermodynamic properties of poly(dG).poly(dC), poly[d(G-C)].poly[d(G-C)], and poly(dG-m5dC).poly(dG-m5dC).

In contrast to poly(dG).poly(dC), which remains in the B-DNA conformation under all experimental conditions the polynucleotides with the strictly alternating guanine/cytosine or guanine/5'-methylcytosine sequences can change from the classical right-handed B-DNA structure to the left-handed Z-DNA structure when certain experimental conditions such as ionic strength or solvent composition are fulfilled. Up to now the investigation of the helix/coil transition of left-handed DNA structures was not possible because the transition temperature exceeds 98 degrees C. By applying moderate external pressure to the surface of the aqueous polymer solution in the sample cell the boiling point of the solvent water is shifted up the temperature scale without shifting the transition temperature, so that we can measure the helix/coil transition of the polynucleotides at all experimental conditions applied. It can thus be shown that the Z-DNA/coil transition is cooperative and reversible. The Tm is 125 degrees C for poly(dG-m5dC).poly(dG-m5dC) in 2mM Mg2+, 50mM Na+, pH 7.2 and 115 degrees c for poly[d(G-C)].poly[d(G-C)] in 3.04M Na+. The transition enthalpy per base pair was determined by the help of an adiabatic scanning microcalorimeter.

DNA↗
PubMedDate not supplied

[Effect of amphotericin B on the activity of synthetic polyribonucleotide interferon inducers].

The authors investigated the intensity of interferon production and the degree of the associated antiviral resistance induced by double-stranded synthetic polyribonucleotide interferon inducers poly(G) . poly(C), poly(G, I) . poly(C) and poly(G, A) . poly(C) in chick embryo cell cultures, continuous diploid human fibroblasts and in mice in the presence of amphotericin B, a macrolide polyene antibiotic enhancing the permeability of plasma membranes for macromolecules. Amphotericin B was found to increase considerably the interferon-inducing and antiviral activity of the above polyribonucleotide complexes in those cell systems where they induced interferon production and antiviral resistance alone, without the antibiotic, but to a lower degree. Amphotericin B did not contribute to the activity of the complexes in those cell systems where they were inert alone. The importance of permeability of the plasma membrane for interferon induction is discussed, and a conclusion is reached that the inertness of the complexes under study in one cell system and their activity in the others are not associated with differences in the permeability of the plasma membranes of different cells for polyribonucleotide interferon inducers.

Amphotericin B↗
PubMedDate not supplied

[Mutagenic activity of synthetic interferon inducers in laboratory mice].

The mutagenic activity of poly(I) . poly(C) and poly(G) . poly(C) complexes in somatic and generative cells of mice was tested. Both preparations exhibited mutagenic activity in both test-systems. The poly(I) . poly(C) complex in the three doses tested was found to be more active both in bone marrow cells and in sex cells of male mice. The maximum effectiveness of this complex was demonstrated upon treatment of postmeiotic cells of males in an intermediate dose of 2.5 mg/kg bw. The rate of induced dominant lethals was 19.1%. In bone marrow metaphases the subtoxic dose of this complex increased 10-fold the control value of structural aberrations. The activity of poly(G) . poly(C) was found to be slightly lower.

Animals↗
PubMedDate not supplied

[Influenza virus sensitivity to interferon and its inducer].

The results of the study on influenza virus sensitivity to interferon of two kinds (human and chicken) and its inducer, poly(G) . poly(C) are presented. Differences in this characteristic among human and animal influenza viruses were demonstrated. There was a correlation between sensitivity to poly(G) . poly(C)-induced interferon and sensitivity to chicken interferon. Comparative studies of sensitivity to interferon in parent viruses and recombinants demonstrated that recombinants derived this property from one of the parental strains.

Animals↗