Poloxamines (Tetronic) are X-shaped amphiphilic block copolymers formed by four arms of poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) blocks bonded to a central ethylenediamine moiety. Such a structure confers multi-responsive behaviour, namely temperature and pH-sensitiveness. At relatively low concentrations but above the critical micellar concentration (CMC), poloxamines generate polymeric micelles. Due to the presence of a hydrophobic core, these nanocarriers are useful in the solubilization and stabilization of poorly water-soluble drugs. Moreover, chemical modification of the micellar core is feasible. These remarkable and unique features, compared to the well-known linear poloxamers, have motivated an increasing interest in the study and application of the branched derivatives in different emerging disciplines. The present review concisely overviews the most important developments comprising the application of poloxamines in drug delivery, mainly as micellar carriers capable of enhancing drug solubility and stability, and also as surface modifiers in the technology of stealth polymeric nanoparticles. Their potential for the administration of drugs by different routes and the improvement of the drug bioavailability and therapeutic effect are discussed.

New cationic pentablock copolymers of poly(diethylaminoethylmethacrylate) (PDEAEM), poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO)--PDEAEM-b-PEO-b-PPO-b-PEO-b-PDEAEM--synthesized in our laboratory were investigated for their potential as non-viral vectors for gene therapy. Agarose gel studies showed that the copolymers effectively condensed plasmid DNA to form polyplexes, and also protected plasmids against nuclease degradation. Light scattering and transmission electron microscopy were used to analyze the apparent size, molecular weight and morphology of these polyplexes. Lactate dehydrogenase assay was employed to find the cytotoxicity limits of the polymers and polyplexes on a human ovarian cancer cell line. The polymers showed much less cytotoxicity than commercially available ExGen 500 (linear polyethyleneimine). By changing the relative lengths of the blocks in the copolymers, it was found that the cytotoxicity of these copolymers could be tailored. The micellar structures of these copolymers in aqueous solutions and their pH-sensitive protonation were added advantages. In vitro transfection efficiencies of the polymers using green fluorescent protein (pEGFP-N1) and luciferase (pRL-CMV) reporter genes were found comparable to ExGen 500. Besides, aqueous solutions of these pentablock copolymers have been shown to exhibit thermodynamic phase transitions and thermoreversible gelation, a quality that could allow subcutaneous/intramuscular injections of these polymers for controlled gene delivery over time.

The purpose of this study was to develop a new monolithic matrix system to completely deliver glipizide, a Biopharmaceutics Classification System (BCS) Class II drug in a zero order manner over an extended time period. Two approaches were examined using drug in formulations that contain swellable hydroxypropylmethylcellulose (HPMC) or erodible polyethylene oxide (PEO). The matrices were prepared by dry blending selected ratios of polymers and ingredients using direct compression technique. Dissolution was assessed using modified USP apparatus II. Glucotrol XL push-pull osmotic pump (PPOP) was used as the reference. The interrelationship between matrix hydration, erosion and textural properties were determined and analyzed under the dissolution test conditions. Linear and reproducible release similar to that of Glucotrol XL was achieved for optimized matrices (f2>50) independent of hydrodynamic conditions. The kinetics of drug delivery was directly related to the synchronization of swelling, erosion and fractional release. HPMC matrices showed a significantly greater degree of hydration and swelling and stronger texture property relative to PEO matrices. Results indicate that in the case of low dose/low soluble drug, total drug release in a zero order manner heavily depends on the synchronization of erosion and swelling fronts during the entire dissolution study.

In a number of applications, e.g. DNA/protein micro-array technology, enzyme-linked immunosorbent assay (ELISA) technology or surface plasmon resonance (SPR) technology, the covalent coupling of proteins to surfaces is required. Following the covalent coupling of proteins, the remaining reactive groups should be blocked in order to avoid covalent binding of the analyte to the reactive surface. To this end, preferably blocking agents containing groups that avoid nonspecific adsorption should be used. These blocking agents are typically ethanolamine and cysteine for protein coupling via amino groups and thiol groups, respectively. This report presents novel blocking agents containing poly(ethylene oxide) (PEO) groups. These blocking agents show enhanced qualities to avoid nonspecific adsorption and can therefore have advantages in versatile protein-surface technologies.

Microencapsulation of the water soluble pesticide monocrotophos (MCR), using polyurethane (PU) as the carrier polymer, has been developed using two types of steric stabilizers, namely PLMA macrodiol and PLMA-g-PEO graft copolymer. The microencapsulation process is carried out in non-aqueous medium and at a moderate temperature to avoid any chemical degradation of monocrotophos during the encapsulation process. Microcapsules were characterized by optical microscopy and SEM for particle size and morphology, respectively. The effects of loading of MCR, crosslinking density of PU, and nature of steric stabilizer on the release of MCR from PU microcapsules have been studied.

Serum response factor (SRF) is a transcription factor required for mesoderm formation in the developing mouse embryo that is important for myogenic differentiation, including notably, the differentiation of the proepicardial organ (PEO) into coronary vascular cells during early development. To identify regulatory sequences that control SRF expression during early mouse development, we used a novel transgenic approach to study the role of conserved noncoding DNA sequences (CNCS) in the SRF gene. Embryonic stem (ES) cells containing a targeted single-copy of putative SRF regulatory sequences were used to directly generate transgenic embryos by tetraploid aggregation. Because the ES cell-derived targeted embryos are genetically equivalent, except for the putative regulatory sequence of interest, differences in transgene expression can be attributed directly to these sequences. Using this approach, we identified an E-box/Ets containing 270-bp cis-acting module in the SRF promoter that mediates expression in the PEO. Reporter transgenes containing this module express in derivatives of the PEO that give rise to the coronary vasculature, but do not express in the PEO-derived epicardium. These results are the first reported in vivo analysis of SRF regulatory elements that control expression during early development. Using this reporter module and this approach, it should be possible to begin to elucidate molecular mechanisms involved in the differentiation of coronary vasculature progenitor cells, as well as identify additional SRF regulatory elements important during mammalian development.

In this paper we have investigated the behavior of core-shell poly(ethylene oxide)-poly(epsilon-caprolactone) (PEO-PCL) micelles derived from copolymers with linear triblock (TR) and 4-arm star-diblock (ST) architectures for the delivery of docetaxel (DTX). DTX was loaded inside micelles (DTX-TR(m) and DTX-ST(m)) with high efficiency and released slowly for more than two weeks. DTX-loaded micelles based on both copolymers had very similar properties in terms of mean size, zeta potential, loading ability and release rate in buffered saline. However, the stability of DTX-ST(m) was very poor in aqueous media with proteins resulting in a strong and progressive aggregation. We studied the effect of increasing concentrations of free DTX or DTX-loaded micelles on growth inhibition of human breast MCF-7 and MDA-MB468 and prostate PC3 and DU145 adenocarcinoma cell lines. DTX-loaded TR micelles induced cell growth inhibition similarly to free DTX whereas DTX-ST(m) showed lower cytotoxicity. On the other hand, by normalizing IC(50) values for the actual amount of DTX released from micelles in the medium, DTX-loaded ST micelles became more active than free DTX in all cell lines tested. Both free DTX and DTX-loaded TR micelles displayed a significantly lower cytotoxic activity in G(2)/M phase synchronized cells, whereas cytotoxicity of DTX-loaded ST micelles did not change. Cytotoxicity was related to micelle stability, uptake and release rate in cell culture media. Our results suggest that for a correct interpretation of cytotoxicity of nanocarriers, the evaluation of their behavior in biologically relevant conditions is of utmost importance to select proper systems for further in vivo testing.

Fungi that cause brown rot of wood are essential biomass recyclers and also the principal agents of decay in wooden structures, but the extracellular mechanisms by which they degrade lignocellulose remain unknown. To test the hypothesis that brown-rot fungi use extracellular free radical oxidants as biodegradative tools, Gloeophyllum trabeum was examined for its ability to depolymerize an environmentally recalcitrant polyether, poly(ethylene oxide) (PEO), that cannot penetrate cell membranes. Analyses of degraded PEOs by gel permeation chromatography showed that the fungus cleaved PEO rapidly by an endo route. 13C NMR analyses of unlabeled and perdeuterated PEOs recovered from G. trabeum cultures showed that a major route for depolymerization was oxidative C---C bond cleavage, a reaction diagnostic for hydrogen abstraction from a PEO methylene group by a radical oxidant. Fenton reagent (Fe(II)/H2O2) oxidized PEO by the same route in vitro and therefore might account for PEO biodegradation if it is produced by the fungus, but the data do not rule out involvement of less reactive radicals. The reactivity and extrahyphal location of this PEO-degrading system suggest that its natural function is to participate in the brown rot of wood and that it may enable brown-rot fungi to degrade recalcitrant organopollutants.

We report a biocompatible polysiloxane containing amphiphilic diblock copolymer, poly(ethylene oxide)-block-poly(gamma-methacryloxypropyltrimethoxysilane) (PEO-b-PgammaMPS), for coating and stabilizing nanoparticles for biomedical applications. Such an amphiphilic diblock copolymer that comprises both a hydrophobic segment with "surface anchoring moiety" (silane group) and a hydrophilic segment with PEO (M(n) = 5000 g/mol) was obtained by the reversible addition-fragmentation chain transfer (RAFT) polymerization using the PEO macromolecular chain transfer agent. When used for coating paramagnetic iron oxide nanoparticles (IONPs), copolymers were mixed with hydrophobic oleic acid coated core size uniformed IONPs (D = 13 nm) in cosolvent tetrahydrofuran. After being aged over a period of time, resulting monodispersed IONPs can be transferred into aqueous medium. With proper PgammaMPS block length (M(n) = 10 000 g/mol), polysiloxane containing diblock copolymers formed a thin layer of coating (approximately 3 nm) around monocrystalline nanoparticles as measured by transmission electron microscopy (TEM). Magnetic resonance imaging (MRI) experiments showed excellent T(2) weighted contrast effect from coated IONPs with a transverse relaxivity r(2) = 98.6 mM(-1) s(-1) (at 1.5 T). Such thin coating layer has little effect on the relaxivity when compared to that of IONPs coated with conventional amphiphilic copolymer. Polysiloxane containing diblock copolymer coated IONPs are stable without aggregation or binding to proteins in serum when incubated for 24 h in culture medium containing 10% serum. Furthermore, a much lower level of intracellular uptake by macrophage cells was observed with polysiloxane containing diblock copolymers coated IONPs, suggesting the reduction of nonspecific cell uptakes and antibiofouling effect.

Tanespimycin (17-allylamino-17-demethoxygeldanamycin or 17-AAG) is a promising heat shock protein 90 inhibitor currently undergoing clinical trials for the treatment of cancer. Despite its selective mechanism of action on cancer cells, 17-AAG faces challenging issues due to its poor aqueous solubility, requiring formulation with Cremophor EL (CrEL) or ethanol (EtOH). Therefore, a CrEL-free formulation of 17-AAG was prepared using amphiphilic diblock micelles of poly(ethylene oxide)-b-poly(D,L-lactide) (PEO-b-PDLLA). Dynamic light scattering revealed PEO-b-PDLLA (12:6 kDa) micelles with average sizes of 257 nm and critical micelle concentrations of 350 nM, solubilizing up to 1.5 mg/mL of 17-AAG. The area under the curve (AUC) of PEO-b-PDLLA micelles was 1.3-fold that of the standard formulation. The renal clearance (CL(renal)) increased and the hepatic clearance (CL(hepatic)) decreased with the micelle formulation, as compared to the standard vehicle. The micellar formulation showed a 1.3-fold increase in the half-life (t(1/2)) of the drug in serum and 1.2-fold increase in t(1/2) of urine. As expected, because it circulated longer in the blood, we also observed a 1.7-fold increase in the volume of distribution (V(d)) with this micelle formulation compared to the standard formulation. Overall, the new formulation of 17-AAG in PEO-b-PDLLA (12:6 kDa) micelles resulted in a favorable 150-fold increase in solubility over 17-AAG alone, while retaining similar properties to the standard formulation. Our data indicates that the nanocarrier system can retain the pharmacokinetic disposition of 17-AAG without the need for toxic agents such as CrEL and EtOH.

Membrane-covered devices could help treat disease of the vasculature such as aneurysm, rupture, and fistulas. They are also investigated to reduce embolic complication associated with revascularization of saphenous vein graft. The aim of this study is to design a clinically applicable biodegradable membrane-covered stent based on the natural polysaccharide chitosan, which has been developed. The mechanical properties of the membrane is optimized through blending with polyethylene oxide (70:30% Wt CH:PEO). The membrane was able to sustain the mechanical deformation of the supporting self-expandable metallic stents during its deployment. The membrane was demonstrated to resist physiological transmural pressure (burst pressure resistance >500 mm Hg) and presented a high-water permeation resistance (1 mL/cm(2) min(-1) at 120 mmHg). The CH-PEO membrane showed a good hemocompatibility in an ex vivo assay. Heparin and hyaluronan surface complexation with the membrane further reduced platelet adhesion by 50.1 and 63% (p = 0.05). The ability of the membrane-covered devices to be used as a drug reservoir was investigated using the nitric oxide donor sodium nitroprusside (SNP). SNP-loaded membranes displayed significantly reduced platelet adhesion.

Preformulation studies were performed on a hemiglutarate ester prodrug of Delta(9)-tetrahydrocannabinol (THC-HG), to facilitate the development of stable formulations by hot-melt methods. The various studies performed included solid-state thermal characterization, pKa, logP, aqueous and pH dependent solubility, pH stability and effect of moisture, temperature and oxygen on solid-state stability. A hot-melt method was utilized to fabricate THC-HG incorporated poly (ethylene oxide) (PEO) matrices and the bioadhesive properties, release profiles and post-processing stability of these matrices were assessed as a function of the polymer molecular weight. The prodrug exhibited a T (g) close to 0 degrees C, indicating its amorphous nature. Thermogravimetric analysis revealed a rapid weight loss after 170 degrees C. The prodrug exhibited a seven-fold higher aqueous solubility as compared to the parent drug (THC). Also, the solubility of the compound increased with increasing pH, being maximum at pH 8. The prodrug exhibited a v-shaped pH-rate profile, with the degradation rate minimum between pH 3 and 4. The moisture uptake and drug degradation increased with an increase in relative humidity. Solid-state stability indicated that the prodrug was stable at -18 degrees C but demonstrated higher degradation at 4 degrees C, 25 degrees C and 40 degrees C (51.6%, 74.5% and 90.1%, respectively) at the end of 3-months. THC-HG was found to be sensitive to the presence of oxygen. The release of the active from the polymeric matrices decreased, while bioadhesion increased, with an increase in molecular weight of PEO.

The bone reaction at the interface of a range of PEO/PBT copolymers (Polyactive) after press-fit implantation in the diaphyseal femur of 20 goats was investigated. The animals were sacrificed at 1, 4, 12, 26, and 52 weeks. Undecalcified histologic sections were prepared, evaluated qualitatively, and quantified with the aid of an image analysis system. The percentage of bone contact was determined morphometrically for all PEO/PBT proportions; for the 70/30 ratio, the percentage of calcification of the material surface and of bone-bonding (defined as a continuum at the light microscopic level between calcification within the material surface and bone tissue) were also assessed. PEO/PBT copolymers possess hydrogelic properties, and a direct relation has been established between water-uptake and PEO content. The swelling behavior of all PEO/PBT substrates resulted in a high degree of bone contact (over 95%) at early stages. From the 12-week survival time onward the 70/30 revealed higher percentages of bone contact (over 80%) when compared with the other ratios (60/40, 55/45, 40/60, and 30/70). This difference was statistically confirmed 1 year postoperatively. The materials with the higher PEO contents showed the highest amounts of calcification, which is reflected by the rate of bone-bonding (70% of bone-bonding for the 70/30 at 52 weeks). Calcification and bone-bonding were not observed for 40/60 and 30/70 proportions. The quantitative results confirmed the relation between PEO content, water-uptake, calcification, and bone-bonding. It was furthermore demonstrated that PEO/PBT copolymers initially establish a high degree of bone contact, whereas the bone-bonding properties, especially of the 70/30, accomplish a long-term implant fixation.

Biodegradable microspheres containing recombinant human Erythropoietin (EPO) were prepared from ABA triblock copolymers, consisting of hydrophobic poly(l-lactic-co-glycolic acid) A blocks and hydrophilic polyethylenoxide (PEO) B blocks. Different polymer compositions were studied for the microencapsulation of EPO using a modified double-emulsion process (W/O/W). The encapsulation efficiency for EPO, ranging from 72% to 99% was quite acceptable. The formation of high molecular weight EPO aggregates, however, was higher than in poly(d,l-lactide-co-glycolide) (PLG) microparticles. Using different excipients with known protein stabilizing properties, such as Bovine Serum Albumin (BSA), Poly-l-Histidine (PH), Poly-l-Arginine (PA) or a combination of PA with Dextran 40 (D40), the EPO aggregate content was significantly reduced to <5% of the encapsulated EPO. In contrast to PLG, ABA triblockcopolymers containing >7 mol % PEO, allowed a continuous release of EPO from microspheres for up to 2 weeks under in-vitro conditions. The release profile was comparable to FITC-Dextran 40 kDa (FD 40) loaded microspheres in the initial release phase, while EPO release was leveling off at later time points. BSA additionally prolonged the EPO release, while blends of PLG and PEO did not generate continuous EPO release profiles. LPLG-PEO-LPLG triblock-copolymers (35 mol % PEO; 30 kDa) in combination with 5% BSA yielded both an acceptable level of EPO aggregates and a continuous release profile under in-vitro conditions for up to 2 weeks. The formation of EPO aggregates at later time points is probably induced by acidic cleavage products of the biodegradable polymer and requires further optimization of the ABA polymer composition.

Recent genetic linkage analyses have mapped the myotonic dystrophy locus to the region of 19q13.2-13.3 lying distal to the gene for creatine kinase subunit M (CKM). The human excision repair gene ERCC1 has also been mapped to this region of chromosome 19. A novel polymorphic DNA marker, pEO.8, has been isolated from a chromosome 19 ERCC1-containing cosmid that maps to a 300-kb NotI fragment encompassing both CKM and ERCC1. Genetic linkage analysis reveals close linkage between pEO.8 and myotonic dystrophy (DM) (zmax = 19.3, theta max = 0.01). Analysis of two key recombinant events suggests a mapping of DM distal to pEO.8 and CKM.

Poly(ethylene oxide sulfide) (PEOS), polymers consisting of an internal ethylene oxide oligomer and disulfide linkage, were synthesized and characterized. The degree of polymerization was dependent upon temperature, dimethyl sulfoxide condition, and monomer hydrophobicity. The stability of PEOS was measured by the size exclusion chromatography method after the incubation both with and without 5 mM glutathione. The disulfide bond was stable in the extracellular condition but completely degraded in 2 h in the reductive cytosolic condition. Hydrophilic PEOS polymers showed no cytotoxicity on the HepG2 cell line. On the basis of these properties, PEOS can be applied in many drug delivery fields.

Thermosensitive poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer, Pluronic F68, containing a hydrophobic unit, oligo-(lactic acid)(oligo-LA) or oligo-caprolactone (oligo-CL), 2-META and RGD as side groups was successfully synthesized and characterized by (1)H NMR, FTIR, and elemental analysis. Their aqueous solution displayed special gel-sol-gel phase transition behavior with increasing temperature from 10 to 70°C, when the polymer concentration was above critical micelle concentration (CMC). The gel-sol phase diagram was investigated using tube inversion method, rheological measurement, and dynamic light scattering. Based on these results, the gelation properties of modified F68 were affected by several factors such as the composition of the substituents, chain length of oligo L-LA or oligo ε-CL, and the concentration of the polymer solutions. The unique phase transition behavior with temperature was observed by modified F68 triblock copolymer, composed of the PPO blocks core and the PEO blocks shell in aqueous solution. This phenomenon was elucidated using (1)H NMR data; the alteration of hydrophobic interaction and chain mobility led to the formation of transparent gel, coexistence of gel-sol, and opaque gel. These hydrogels may be useful in drug delivery and tissue engineering.

Cell osmotic water permeability, Pcos, of the peritubular aspect of the proximal convoluted tubule (PCT) was measured from the time course of cell volume changes subsequent to the sudden imposition of an osmotic gradient, delta Cio, across the cell membrane of PCT that had been dissected and mounted in a chamber. The possibilities of artifact were minimized. The bath was vigorously stirred, the solutions could be 95% changed within 0.1 s, and small osmotic gradients (10-20 mosM) were used. Thus, the osmotically induced water flow was a linear function of delta Cio and the effect of the 70-microns-thick unstirred layers was negligible. In addition, data were extrapolated to delta Cio = 0. Pcos for PCT was 41.6 (+/- 3.5) X 10(-4) cm3 X s-1 X osM-1 per cm2 of peritubular basal area. The standing gradient osmotic theory for transcellular osmosis is incompatible with this value. Published values for Pcos of PST are 25.1 X 10(-4), and for the transepithelial permeability Peos values are 64 X 10(-4) for PCT and 94 X 10(-4) for PST, in the same units. These results indicate that there is room for paracellular water flow in both nephron segments and that the magnitude of the transcellular and paracellular water flows may vary from one segment of the proximal tubule to another.

BACKGROUND

The persistence of dermal fillers containing crosslinked hyaluronic acid (XLHA) correlates linearly to the concentration of polymer in solution. For dermal fillers composed of XLHA, a polymer concentration above approximately 25 mg/mL is not practical because it cannot be easily injected through a small-bore needle.

OBJECTIVE

Formulating dermal fillers from mixtures of carboxymethylcellulose (CMC) and polyethylene oxide (PEO) has several advantages over XLHA. We hypothesize that increasing the concentration of CMC/PEO will increase the persistence in the dermis. These polymers of CMC and PEO can be formulated at higher concentrations than XLHA to produce smooth, particulate-free gels resulting in easier, more controllable injection. Second, these gels are not required to be covalently crosslinked; CMC/PEO forms a stable gel-like structure in solution without crosslinking.

METHODS

Here we have prepared dermal fillers from CMC/PEO polymer blends at concentrations of 20 mg/mL (dermal filler 1), 29 mg/mL (dermal filler 2), 37 mg/mL (dermal filler 3), and 45 mg/mL (dermal filler 4) and measured their rheologic properties compared to commercial XLHA dermal fillers.

CONCLUSIONS

The data here demonstrate that it is possible to duplicate the rheologic properties of commercial XLHA fillers using CMC/PEO at different polymer concentrations to formulate improved dermal fillers. All of the dermal filler formulations prepared can be easily injected through 30-gauge needles.

The work presented here focuses on the development of a method adapting isotope labeling of proteins with ICAT to the study of highly hydrophobic proteins. Conditions for the labeling of proteins were first established using two standard soluble proteins and iodoacetamidyl-3,6-dioxaoctanediamine biotin (PEO-iodoacetyl biotin). Results demonstrated the efficiency of the labeling in the presence of high concentrations of both SDS and urea. These conditions were then used to label a highly hydrophobic mitochondrial membrane protein, the adenine nucleotide translocator ANT-1, with PEO-iodoacetyl biotin and then with the cleavable ICAT reagent. The results presented here show that labeling of proteins with cleavable ICAT is possible and may even be improved in strong denaturing buffers containing both SDS at a concentration higher than 0.5% (w/v) and urea. These results open the possibility of applying the ICAT strategy to complex samples containing very hydrophobic proteins solubilized in urea-SDS buffers. The adaptability of the developed method is demonstrated here with preliminary results obtained during the study of membrane-enriched fractions prepared from murine embryonic stem cells.

Nanodomains formed by microphase separation in thin films of the diblock copolymers poly(styrene-b-2-vinylpyridine) (PS-b-P2VP) and poly(styrene-b-ethyleneoxide) (PS-b-PEO) were imaged by means of infrared scattering-type near-field microscopy. When probing at 3.39 mum (2950 cm(-1)), contrast is obtained due to spectral differences between the C--H stretching vibrational resonances of the respective polymer constituents. An all-optical spatial resolution better than 10 nm was achieved, which corresponds to a sensitivity of just several thousand C--H groups facilitated by the local-field enhancement at the sharp metallic probe tips. The results demonstrate that infrared spectroscopy with access to intramolecular dimensions is within reach.

In vitro protein adsorption, platelet adhesion and activation on new hydrogel surfaces, composed of poly(ethylene oxide) (<em>PEO</em>) and poly(tetramethylene oxide) (PTMO) or poly(dimethyl siloxane) (PDMS), were investigated. By varying <em>PEO</em> length (MW = 2000 or 3400), hydrophobic components (PTMO or PDMS) or polymer topology (block or graft copolymers), various physical hydrogels were produced. Their structures were verified by 1H NMR and ATR-IR and the molecular weights were determined by gel permeation chromatography. The hydrogels were soluble in a variety of organic solvents, while absorbed a significant amount of water with preserved three-dimensional structure by physical crosslinking. The dynamic contact angle measurement revealed that the surface hydrophilicity increased by incorporating longer <em>PEO</em>, <em>PEO</em> grafting, and adopting PDMS as a hydrophobic segment instead of PTMO. It was observed from in vitro protein adsorption study that the hydrogels exhibited significantly lower adsorption of human serum albumin (HSA), human fibrinogen (HFg), and IgG, when compared with Pellethane, a commercial polyurethane taken as a control. The hydrogels were attractive for HSA but not sensitive to HFg and IgG. And more than 65% of the proteins detected on the surfaces of the hydrogels were reversibly detached by being treated with an SDS solution. It was evident that the hydrogels synthesized in this study were much more resistant to platelet adhesion than the control, which might depend on the composition of proteins adsorbed on the surfaces and their degree of denaturation. Among the hydrogels tested, <em>PEO</em>3,4kPDMS exhibited albumin-rich and platelet-resistant surfaces, implying a potential candidate for biomaterial.

The effect of ligand structure on the magnetic resonance (MR) imaging and biodistribution of six gadolinium (Gd) chelates based on a hydroxypyridonate-terephthalimide (HOPO-TAM) ligand design was investigated. Modifications to the molecular structure of the Gd-HOPO-TAM chelates (hydrophilicity and aromatic group substitution) significantly influence the efficacy of imaging and biodistribution. MR imaging was performed on female mice after intravenous (iv) injection of 100 micromol of Gd/kg of body weight of the different complexes. The biodistribution results indicate that the liver uptake of the complexes is enhanced by a short poly(ethyleneoxy) (PEO) chain, while blood pool localization is facilitated by a very long PEO chain. There is a direct correlation between the blood pool localization of the complexes and the signal intensity of blood vessels in the MRI. The imaging results are consistent with in vitro NMR measurements that indicate long PEO chains increase image enhancement capabilities in the presence of serum albumin.

According to experimental models suggesting that overproduction of oxygen free-radicals may occur when the electron transport in the respiratory chain is impaired, we searched for in vivo biological markers of oxidative stress in 11 patients affected by histologically proven mitochondrial myopathy with progressive external ophthalmoplegia (PEO) and partial cytochrome c oxidase deficiency in muscle fibres. Six of the patients carried large-scale deletions of mitochondrial DNA. Biochemical assays included the determination of plasma and erythrocyte reduced glutathione (GSH) concentration, plasma malondialdehyde, fluorescent adducts of aldehydes with plasma proteins, and serum level of lipid peroxides. In patients with PEO the mean values of lipid peroxides and of the fluorescent adducts of aldehydes with plasma proteins were significantly higher with respect to normal controls, while the mean values of plasma and erythrocyte GSH concentration were significantly lower. The reported data indicate an increase of lipid peroxidation indexes along with the reduction of one of the most important antioxidant systems and suggest the hypothesis that overproduction of reduced oxygen species might be an adjunctive cause of cell damage in mitochondrial myopathies and encephalomyopathies associated with defects of oxidative phosphorylation.