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Adsorption of the quinolone antibiotic nalidixic acid onto anion-exchange and neutral polymers.

Pharmaceutical products are being found in surface and ground waters around the world. While the consequences to human health are unknown, it is suspected that these contaminants adversely alter aquatic ecosystems. This study presents adsorption results for one pharmaceutical product, nalidixic acid (NA), on neutral and anion-exchange polymers at three pH values. The adsorption of NA below and above its pKa of approximately 6 on polymers with different matrices, forms, and degrees of polarity were evaluated. By comparing the Freundlich constants KF and n, the results show that the neutral form of NA adsorbs to a greater extent on neutral polymers, and that the anionic form of NA adsorbs more to anion-exchange polymers. Also, results of the adsorption experiments suggest that aromatic ring interactions between NA and the surface of both neutral and anion-exchange polymers are important in the adsorption process. These results have important implications for the treatment of pharmaceutical-contaminated water, as many pharmaceutical contaminants are ionizable and have aromatic rings in their structure. This study illustrates the importance of pH and sorbate and sorbent structure in considering polymer sorption for treatment of pharmaceutical-contaminated aqueous systems.

Adsorption↗

Developments in the use of soluble ionic polymers as pseudo-stationary phases for electrokinetic chromatography and stationary phases for electrochromatography.

This article reviews the development, characterization and application of soluble ionic polymeric materials as pseudo-stationary phases for electrokinetic chromatography and as stationary phases for electrochromatography since 1997. Polymeric pseudo-stationary phases for electrokinetic chromatography, including cationic polymers, anionic siloxane and acrylamide polymers, polymerized surfactants (micelle polymers), and chiral polymers are reviewed. Also reviewed are suspended molecularly imprinted polymer micro-particles. Application of polymeric pseudo-stationary phases with electrospray ionization mass spectrometric detection is presented. Recent progress in the development and characterization of physically adsorbed stationary phases for electrochromatography using polymers of the same or similar chemistry is also reviewed.

Chromatography, Micellar Electrokinetic Capillary↗

Nanoclusters in polymer matrices prepared by co-deposition from a gas phase.

This paper reviews the fabrication of organic and metal nanoclusters in polymer matrices by three co-deposition techniques. In particular, the structure and properties of polytetrafluoroethylene (PTFE), polychlortrifluoroethylene (PCTFE), polyparaphenylene sulphide (PPS), polystyrene (PS) and polyparaxylylene (PPX) films, containing gold (Au) and dye clusters are discussed. For the first time, dye-filled polymers and multi-component films, consisting of both Au nanoparticles and dye molecules, dispersed in the PTFE matrix were studied. A low temperature plasma was used for film structure modification. Cluster formation process was studied using optical spectroscopy in situ. Transmission electron microscopy (TEM), atomic force microscopy (AFM) and ellipsometry were used for characterisation of the grown films. During Au-PTFE film growth plasmon band shifted from 460-480 nm to 560 nm. Au cluster diameter was in the 3-7 nm range. Plasma treatment of the vapours led to formation of smaller, but more aggregated clusters. During Au-PPS film deposition a two-step growth mechanism was discovered. At the beginning of film growth the plasmon band at 540 nm appeared, but as thickness increased, the band at 430 nm dominated. Without plasma treatment a disordered mixture was deposited, while with plasma treatment large Au aggregates confined with PPS matrix having plasmon band at 620 nm were formed. Dye cluster formation depends on the dye ability to aggregate, its concentration and the properties of the polymer matrix. But cluster formation can also be tuned by varying the deposition conditions. Laser beam evaporation promoted cluster formation, while plasma treatment and dilution in a polymer matrix prevented cluster formation. In all cases both equilibrium and non-equilibrium film structure can be formed using kinetic factor. Asymmetric molecules with bulky substituents were oriented in polymer matrices by applying an electric field in situ or by corona poling. These molecules did not aggregate even at high dye load. The films exhibited second harmonic generation, which demonstrated chromophore orientation in the polymer matrices.

Coloring Agents↗

Biocatalysis in the development of functional polymer-ceramic nanocomposites.

Fluorescent silica/polymer nanocomposites have been synthesized by condensing tetramethyl orthosilicate (TMOS) around fluorescent polymer strands of poly(2-naphthol). The polymer is biocatalytically synthesized via peroxidase catalyzed polymerization in micelles of the cationic surfactant, cetyltrimethylammonium bromide (CTAB). Silica condensation at the micelle-water interface results in encapsulation of the polymer. Fluorescence spectroscopy and fluorescent light microscopy provide critical evidence that the polymer luminescence properties are conferred to the composite material. The fabrication of polymer entrapped in ordered, mesoporous materials represents a viable step toward the development of functional polymer-ceramic nanocomposites.

Catalysis↗

Chitosan based surfactant polymers designed to improve blood compatibility on biomaterials.

We developed chitosan based surfactant polymers that could be used to modify the surface of existing biomaterials in order to improve their blood compatibility. These polymers consist of a chitosan backbone, PEG side chains to repel non-specific protein adsorption, and hexanal side chains to facilitate adsorption and proper orientation onto a hydrophobic substrate via hydrophobic interactions. Since chitosan is a polycationic polymer, and it is thrombogenic, the surface charge was altered to determine the role of this charge in the hemocompatibility of chitosan. Charge had a notable effect on platelet adhesion. The platelet adhesion was greatest on the positively charged surface, and decreased by almost 50% with the neutralization of this charge. A chitosan surface containing the negatively charged SO(3)(-) exhibited the fewest number of adherent platelets of all surfaces tested. Coagulation activation was not altered by the neutralization of the positive charge, but a marked increase of approximately 5-6 min in the plasma recalcification time (PRT) was displayed with the addition of the negatively charged species. Polyethylene (PE) surfaces were modified with the chitosan surfactant resulting in a significant improvement in blood compatibility, which correlated to the increasing PEG content within the polymer. Adsorption of the chitosan surfactants onto PE resulted in approximately an 85-96% decrease in the number of adherent platelets. The surfactant polymers also reduced surface induced coagulation activation, which was indicated by the PEG density dependent increase in PRTs. These results indicate that surface modification with our chitosan based surfactant polymers successfully improves blood compatibility. Moreover, the inclusion of either negatively charged SO(3)(-) groups or a high density of large water-soluble PEG side chains produces a surface that may be suitable for cardiovascular applications.

Adsorption↗

Dual mode bioreactions on polymer nanoparticles covered with phosphorylcholine group.

We investigated the preparation of polymer nanoparticles covered with phosphorylcholine (PC) groups and the immobilization of proteins in order to observe dual mode bioreactions on the nanoparticles. For the surface modification on the nanoparticles, a water-soluble amphiphilic phospholipid polymer with PC groups as a hydrophilic moiety was synthesized. In this polymer, an active ester group, which can immobilize proteins, was introduced. Using the phospholipid polymer as a solubilizer, poly(L-lactic acid) nanoparticles were prepared from its methylene chloride solution in an aqueous medium by the solvent evaporation method. The diameter of the nanoparticles was ca. 200 nm and the surface was covered with the PC groups and active ester groups. Proteins could immobilize on the nanoparticles under mild conditions by the reaction between the active ester group and amino group in the proteins. Both an antibody and enzyme were immobilized on the nanoparticles and bioreactions such as the antigen/antibody reaction and enzymatic reaction were observed. When an antigen was added to the suspension of the nanoparticles, aggregation of the nanoparticles occurred and then they precipitated. Also, the enzymatic reaction proceeded well when the enzyme substrate was added to the suspension. Based on these results, we provided polymer nanoparticles functionalized with both the antibody and enzyme, and the dual mode bioreactions could occur. We concluded that the novel polymer nanoparticles could be used for nano-/micro-scaled diagnostic and medical treatment systems.

Antibodies, Monoclonal↗

Lignin-polymer blends: evaluation of compatibility by image analysis.

This paper opens onto a general discussion on the development of new polymeric materials obtained from lignin blends. The aim is (i) to look for good polymer candidates to obtain a good compatibility with lignins (that is among semi polar polymers), and (ii) to look for good lignin candidates to obtain a good compatibility with polymers showing extreme behaviours (very polar, e.g. starch, or apolar, e.g. polypropylene). The compatibility is simply assessed through the blend morphology, as studied by visible microscopy. The morphology of the blends obtained from semi polar polymers is very sensitive to the variation of the solubility parameters. In a low range of polymer solubility parameters (delta delta = 1 cal cm(-3)), both heterogeneous and homogeneous systems are obtained. These blends could be easily improved by a careful choice in the polymer structure (particularly in the family of biodegradable polyesters); it could be possible also to take advantage of lignin variability to improve the compatibility. Only low molecular weight lignins are compatible with apolar and very polar matrixes. These compounds induce interesting specific properties, and original methods have to be looked for in order to improve their production.

Lignin↗

Quantitative evaluation of polymer concentration profile during swelling of hydrophilic matrix tablets using 1H NMR and MRI methods.

Many pharmaceutical tablets are based on hydrophilic polymers, which, after exposure to water, form a gel layer around the tablet that limits the dissolution and diffusion of the drug and provides a mechanism for controlled drug release. Our aim was to determine the thickness of the swollen gel layer of matrix tablets and to develop a method for calculating the polymer concentration profile across the gel layer. MR imaging has been used to investigate the in situ swelling behaviour of cellulose ether matrix tablets and NMR spectroscopy experiments were performed on homogeneous hydrogels with known polymer concentration. The MRI results show that the thickest gel layer was observed for hydroxyethylcellulose tablets, followed by definitely thinner but almost equal gel layer for hydroxypropylcellulose and hydroxypropylmethylcellulose of both molecular weights. The water proton NMR relaxation parameters were combined with the MRI data to obtain a quantitative description of the swelling process on the basis of the concentrations and mobilities of water and polymer as functions of time and distance. The different concentration profiles observed after the same swelling time are the consequence of the different polymer characteristics. The procedure developed here could be used as a general method for calculating polymer concentration profiles on other similar polymeric systems.

Cellulose↗

Modeling of swelling and drug release behavior of spontaneously forming hydrogels composed of phospholipid polymers.

Physically cross-linked hydrogel had been investigated in order to make use of oral polypeptide drug delivery carrier. By using 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer, we had prepared a spontaneously forming hydrogel showing controllable dissociation via pH changes. In this study, the dissociation and release of polypeptide drugs from the MPC polymer hydrogel loaded with polypeptide drugs, which had been prepared from aqueous solutions containing water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB) had been executed. The polymer concentration was 10 wt.% and PMA/PMB feed ratio (A/B feed ratio) was 5/5. Insulin labeled with fluorescein-4-isothiocyanate (FITC) and cytochrome c had been loaded for the examination of the release behavior. The hydrogel in pH 1.8 aqueous solution would be swelling, for the hydrogel would absorb outside water. However, during this process, the polymer is dissoluting out from the hydrogel due to the widening of the polymer network. The cytochrome c followed anomalous transport while insulin depended on the swelling and dissolution of the polymer chains. The hydrogel showed surface erosion in neutral condition, although the hydrogel is composed of two different polymer possessing divergent physical properties. The release followed anomalous transport, but the erosion rate slightly changed with as the hydrophobicity of the loaded drugs. The total amount of the drugs released in neutral condition was larger compared to the acidic condition. When the eroded percentage and the release percentage were compared with each other, it showed that release was slightly slower than erosion, indicating that the erosion was controlling the release phenomenon.

Cytochromes c↗

Synthesis and study of controlled release of ibuprofen from the new acrylic type polymers.

New acrylic type polymeric systems having degradable ester bonds linked to ibuprofen were synthesized and evaluated as materials for drug delivery. Methacryloyloxy(2-hydroxy)propyl-4-isobutyl-alpha-methylphenyl acetate (MOPE), a new methacrylic derivative of ibuprofen in which the drug is separated from the methacrylic backbone by an oxy(2-hydroxy)propylene spacer arm and hydrolytically labile ester bond, was synthesized from reaction of glycidyl methacrylate with ibuprofen. The resulting drug containing monomer was copolymerized with methacrylamide, 2-hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or n-butyl methacrylate by free radical polymerization method in N,N-di-methylformamide (DMF) solution, utilizing azobisisobutyronitrile as initiator at the temperature range 65-70 degrees C. The obtained polymers were characterized by FT-IR, 1H NMR and 13C NMR spectroscopy. Gel permeation chromatography (GPC) was used for determination of average molecular weights of drug-polymer conjugates and showed that the polydispersity indices of the polymers are in the range of 1.9-2.3. Drug release studies were performed by hydrolysis in buffered solutions (pH 1 and 8) at 37 degrees C. Detection of hydrolysis by UV spectroscopy at selected interval showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behavior of polymeric prodrugs is strongly based on the hydrophilicity of polymer and the pH of the hydrolysis solution. The hydrophilic polymers containing ibuprofen were hydrolyzed in buffer solutions rather than the hydrophobic polymers.

Acrylates↗

Use of molecularly imprinted polymers from a mixture of tetracycline and its degradation products to produce affinity membranes for the removal of tetracycline from water.

The possibility of introducing multiple recognition in artificial receptors by imprinting polymers, using a mixture of tetracycline (TC) and its degradation products as templates, has been examined. The recognition ability of the resulting molecularly imprinted polymer (MIP), as evaluated by batch rebinding assay, was found to be group-specific to tetracyclines, while the single tetracycline imprinted polymer (MIP-2) prepared using TC free from degradation products as the print molecule showed considerably high selectivity for doxycycline (DC) and modest selectivity for TC and other TC derivatives, oxytetracycline (OTC) and chlortetracycline (CTC). Based on the recognition property of the multiple tetracycline imprinted polymer (MIP-1), the polymer was applied in affinity membrane extraction as a class-selective adsorption phase to remove tetracyclines residues from water. For this purpose, the ground MIP was incorporated in a plasticized poly(vinyl chloride)-membrane by casting method. Affinity separation of the obtained membrane was evaluated for the extraction of tetracycline and its analogs (CTC, OTC or DC) in aqueous solutions by a dialysis method. The membrane exhibited significantly stronger extraction ability towards tetracycline and structurally related compounds than a "blank" membrane having a non-printed polymer (NIP) as the adsorption phase. The result of these membrane extraction studies also indicates that the drug saturating at the receptor sites of MIP (deposited in membrane) faster will also be released into the receptor chamber faster. These affinity membranes were able to extract tetracyclines from water at all pHs, the highest selectivity being shown at pH 7 of the feed solution, which gives the lowest flux of the drug. Moreover, presence of salt in the feed solution increases the release of tetracycline bound in membrane. The results of the present study show that imprinting simultaneous with TC and TC degradation products formed in situ as a mixture template generates the group selectivity towards tetracyclines for the polymeric material. High affinity to a class of tetracycline of the membrane fabricated with this receptor, together with its fast and simple MIP fabrication, provides good possibilities for its application in separation processes of tetracycline antibiotics, which often contaminate the aqueous environment.

Hydrogen-Ion Concentration↗

Polymer-surfactant and protein-surfactant interactions.

The phase behavior and some physicochemical properties of homopolymers (HP) and hydrophobically modified (HMP) polymers, as well as of polyelectrolytes (PE) and proteins (PR), in the presence of aqueous surfactants, or their mixtures, are discussed. Mixing the above components gives rise to the formation of organized phases, whose properties are controlled by polymer and/or surfactant content, temperature, pH, and ionic strength. Depending on the nature, concentration, and net charge of both solutes, molecular solutions, polymer-surfactant complexes, adsorption onto micelles and vesicles, gels, liquid crystalline phases, and precipitates are observed. Such rich polymorphic behavior is the result of a complex balance between electrostatic, excluded volume, van der Waals, and other contributions to overall system stability. It is also modulated by the molecular details and architecture of both the polymer and the surfactant. Different experimental methods allow investigation of the above systems and getting information on the nature of polymer-surfactant interactions (PSI). Surface adsorption and thermodynamic methods, together with investigation of the phase diagrams, give information on the forces controlling PSI and on the existence of different phases. Conductivity, QELS and viscosity allow estimating the size and shape of polymer-surfactant (protein-surfactant) complexes. Optical microscopy, cryo-TEM, AFM, NMR, fluorescence, and relaxation methods give more information on the above systems. Use of the above mixtures in controlling gelation, surface covering, preparing dielectric layers, and drug release is suggested.

Chemical Phenomena↗

Preparation and colloidal stability of monodisperse magnetic polymer particles.

A previously proposed method was examined for producing monodisperse, submicrometer-sized magnetic polymer particles. The method applies soap-free emulsion polymerization during which Fe3O4 magnetic nanoparticles are heterocoagulated onto precipitated polymer nuclei. To chemically fix the magnetic particles to the polymer nuclei, vinyl groups were introduced on the Fe3O4 particles in a preliminary surface modification reaction with methacryloxypropyltrimethoxysilane, and methacryloxypropyldimethoxysilane (MPDMS) was added to reaction systems of the soap-free emulsion polymerization. The colloidal dispersion stability of magnetic polymer particles was improved by the addition of an ionic monomer, sodium p-styrenesulfonate (NaSS), during the polymerization. The polymerizations were carried out with styrene monomer and potassium persulfate initiator in ranges of NaSS concentrations (0-2.4 x 10(-3) M), NaSS addition times (60-80 min), and monomer concentrations (0.3-0.6 M) at fixed concentrations of 1.6 x 10(-2) M initiator and 1.3 x 10(-2) M MPDMS for pH 4.5 adjusted with a buffer system of [CH3COOH]/[NaOH]. The addition of NaSS during the polymerization could maintain the dispersion stability of magnetic polymer particles during the polymerization. Selection of the reaction conditions enabled the preparation of colloidally stable, submicrometer-sized magnetic polymer particles that had coefficients of variation of distribution smaller than the standard criterion for monodispersity, 10%.

Colloids↗

Feasibility study on the retention of superporous hydrogel composite polymer in the intestinal tract of man using scintigraphy.

In recent years, many complex oral drug delivery systems have been developed using various polymers in order to achieve better drug targeting and drug absorption in the intestinal tract. Superporous hydrogel (SPH) and SPH composite (SPHC)-based drug delivery systems were also developed for the targeted delivery of peptide drugs into the intestinal tract. In the present study, the retention time of SPHC polymer is studied in man using the scintigraphy technique. To that purpose, SPHC polymers were radiolabelled with Tc-99m and administered orally in an enteric-coated gelatin capsule. The location of the radiolabelled polymer was monitored in five healthy volunteers while the subjects were sitting in front of a large field of view gamma camera. The results showed that enteric-coated gelatin capsules remained in the stomach for 75 to 150 min after oral administration to fasted volunteers and that the SPHC polymers thereafter attached to the upper part of the small intestine for at least 45 to 60 min due to their mechanical fixation properties. No discomfort was observed in any of the volunteers after oral administration of these polymers, which indicates that they are safe to be applied for oral drug delivery systems in man.

Administration, Oral↗

Rational design of composition and activity correlations for pH-sensitive and glutathione-reactive polymer therapeutics.

Limited cytoplasmic delivery of enzyme-susceptible drugs remains a significant challenge facing the development of protein and nucleic acid therapies that act in intracellular compartments. "Smart" pH-sensitive, membrane-destabilizing polymers present an attractive approach to shuttle therapeutic molecules past the endosomal membrane and into the cytoplasm of targeted cells. This report describes the use of a new functionalized monomer, pyridyl disulfide acrylate (PDSA), to develop pH-sensitive, membrane-destabilizing, and glutathione-reactive polymers by copolymerization with several pH-sensitive and hydrophobic monomers. The activity of the carriers is described as a function of (a) the influence of increasing the length of the hydrophobic alkyl group substituted onto the pH-sensitive monomer and (b) of the effect of incorporating a hydrophobic monomer such as butyl acrylate (BA) on the pH sensitivity and membrane-destabilizing activity of new polymer compositions. The membrane-destabilizing activity of different polymer compositions was evaluated as a function of pH and polymer concentration using the red blood cells (RBC) hemolysis assay. Hemolysis results show that the increase in the hydrophobic character of polymer backbone results in a shift in the pH sensitivity profile and an increase in the membrane-destabilizing activity. Results show that the observed hemolytic activities and pH sensitivity profiles could be designed across a range that matches the properties needed for drug carriers to enhance the cytoplasmic delivery of therapeutic cargos.

Acrylates↗

Rational design of composition and activity correlations for pH-responsive and glutathione-reactive polymer therapeutics.

Limited cytoplasmic delivery of enzyme-susceptible drugs remains a significant challenge facing the development of protein and nucleic acid therapies that act in intracellular compartments. "Smart" pH-responsive, membrane-destabilizing polymers present a new approach to shuttling therapeutic molecules past the endosomal membrane and into the cytoplasm of targeted cells. This report describes the use of a functionalized monomer, pyridyl disulfide acrylate (PDSA), to develop pH-responsive, membrane-destabilizing, and glutathione-reactive polymers by copolymerization with several pH-responsive and hydrophobic monomers. The activity of the carriers is described as a function of (a) increasing the length of the hydrophobic alkyl group substituted onto the pH-responsive monomer and (b) the incorporation of a hydrophobic monomer such as butyl acrylate (BA) on the pH sensitivity and membrane-destabilizing activity of new polymer compositions. The membrane-destabilizing activity of different polymer compositions was evaluated as a function of pH and polymer concentration using the red blood cell (RBC) hemolysis assay. Hemolysis results show that the increase in the hydrophobic character of the polymer backbone results in a shift in the pH sensitivities and an increase in the membrane-destabilizing activity. Results show that the observed hemolytic activities and pH sensitivity profiles could be designed across a range that matches the properties needed for enhancing the cytoplasmic delivery of macromolecular therapeutic.

Acrylates↗

Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery.

To overcome the skin's barrier properties that block transdermal delivery of most drugs, arrays of microscopic needles have been microfabricated primarily out of silicon or metal. This study addresses microneedles made of biocompatible and biodegradable polymers, which are expected to improve safety and manufacturability. To make biodegradable polymer microneedles with sharp tips, micro-electromechanical masking and etching were adapted to produce beveled- and chisel-tip microneedles and a new fabrication method was developed to produce tapered-cone microneedles using an in situ lens-based lithographic approach. To replicate microfabricated master structures, PDMS micromolds were generated and a novel vacuum-based method was developed to fill the molds with polylactic acid, polyglycolic acid, and their co-polymers. Mechanical testing of the resulting needles measured the force at which needles broke during axial loading and found that this failure force increased with Young's modulus of the material and needle base diameter and decreased with needle length. Failure forces were generally much larger than the forces needed to insert microneedles into skin, indicating that biodegradable polymers can have satisfactory mechanical properties for microneedles. Finally, arrays of polymer microneedles were shown to increase permeability of human cadaver skin to a low-molecular weight tracer, calcein, and a macromolecular protein, bovine serum albumin, by up to three orders of magnitude. Altogether, these results indicate that biodegradable polymer microneedles can be fabricated with an appropriate geometry and sufficient strength to insert into skin, and thereby dramatically increase transdermal transport of molecules.

Biocompatible Materials↗

Cationic polymers that enhance the performance of HbsAg DNA in vivo.

In this paper, different cationic polymers were investigated as a DNA delivery system both in vitro in dendritic and muscle cells and in vivo, in a murine model. Expression of the reporter gene beta-galactosidase was used in order to determine the in vitro transfection efficiency of these polymer-DNA complexes (polyplexes) and both specific mRNA and protein expression were monitored in parallel with polyplex toxicity on the cells. Interestingly, the enhancing expression activities of the different polyplexes were tissue-dependent, implying that they may gain entrance to the cells through specific receptors. Subsequently, complexes of polymers and DNA plasmid (pCMV-S) encoding the human hepatitis B virus (HBV) surface antigen (HBsAg) were injected into the skeletal muscles of BALB/c mice. Higher levels of both HBsAg local expression in the tibial anterior muscles and systemic humoral immune responses were detected when the selected polymers complexed with pCMV-S were compared to those complexed with pCMV-S alone. Induction of immunoglobulin G2a (IgG2a) against HbsAg in the serum of pCMV-S-polyplex vaccinated mice varied with the polymer used, suggesting that polyplex-mediated DNA vaccination can potentially modulate the type of helper T cell immunity (Th). The effect of some polyplexes to switch the host immune response more towards a Th1 response may be associated with their differential efficiency to transfect dendritic cells and/or other antigen-presenting cells (APC) as was observed in vitro. These results suggest that the investigated cationic polymers can be effective as delivery/adjuvant compounds for DNA.

Adjuvants, Immunologic↗