Mg-Zn-Ca alloys are considered as suitable biodegradable metallic implants because of their biocompatibility and proper physical properties. In this study, we investigated the effect of Zn concentration of Mg-xZn-0.3Ca (x=1, 3 and 5wt.%) alloys and surface modification by plasma electrolytic oxidation (PEO) on corrosion behavior in in vivo environment in terms of microstructure, corrosion rate, types of corrosion, and corrosion product formation. Microstructure analysis of alloys and morphological characterization of corrosion products were conducted using x-ray computed tomography (micro-CT) and scanning electron microscopy (SEM). Elemental composition and crystal structure of corrosion products were determined using x-ray diffraction (XRD) and electron dispersive x-ray spectroscopy (EDX). The results show that 1) as-cast Mg-xZn-0.3Ca alloys are composed of Mg matrix and a secondary phase of Ca2Mg6Zn3 formed along grain boundaries, 2) the corrosion rate of Mg-xZn-0.3Ca alloys increases with increasing concentration of Zn in the alloy, 3) corrosion rates of alloys treated by PEO sample are decreased in in vivo environment, and 4) the corrosion products of these alloys after in vivo tests are identified as brucite (Mg(OH)2), hydroxyapatite (Ca10(PO4)6(OH)2), and magnesite (MgCO3·3H2O).

Polyethylene oxide (PEO) surfaces were prepared by the addition of PEO- and sulfonated PEO-containing amphiphilic block copolymers as surface-modifying additives in a segmented polyurethane (PU). PEO-PPO-PEO triblock copolymers (Pluronics) with different PEO chain lengths (from 2 to 80) were used as additives. The prepared film surfaces were characterized by the measurement of dynamic water contact angles and electron spectroscopy for chemical analysis. It was observed that the PU films containing 10 wt% of PEO additives were surface-saturated with the additives regardless of their PEO chain length, but the PEO chains were more projected from the film surfaces containing the additives with longer PEO chains. The water absorption of the films increased largely with the increasing PEO chain length of the additives. The addition of PEO additives produced film surfaces that were in a gel-like state. The films demonstrated some extraction of the PEO additives. However, the additives with higher molecular weights were entrapped more stably into the PU matrix. The mechanical properties (tensile strength and elongation) of the films were changed by the addition of PEO additives, but the differences were not significant compared to the control PU. The platelet adhesion on the film surfaces decreased with increasing PEO chain length of the additives. The film surface containing additives with long PEO chains (chain length of 80) was particularly effective in preventing platelet adhesion. The effect of negatively charged sulfonate groups on the prevention of platelet adhesion appeared only on the film surfaces containing additives with short PEO chains. For longer PEO chains, the chain mobility effect was more dominant than the negative charge effect on the prevention of platelet adhesion.

The solubility enhancement of poorly soluble compounds is an important task in pharmaceutical technology as it leads to better bioavailability and a more efficient application. Fused dispersions (FDs) of simvastatin (SIM) using PEO-PPO block copolymer were prepared which paved the way for the formation of an amorphous product with enhanced dissolution and bioavailability. The accumulative solubility of simvastatin (SIM) from PEO-PPO block copolymer (Lutrol NF 127 prill surfactant) was found to be superior to the drug alone which may be due to the increased oxyethylene content that played the major role in solubility enhancement. A 3(2) full factorial approach was used for optimization wherein the temperature to which the melt-drug mixture cooled (X1) and the drug-to-polymer ratio (X2) were selected as the independent variables and the time required for 90% drug dissolution (t90%) was selected as the dependent variable. A low level of X1 and a high level of X2 were suitable for obtaining higher dissolution of SIM from SIM FDs. On increasing melt to cool drug temperature, t90% increased thus improving dissolution rate of FD2 batch with the maximum drug release (99.63%) in 120 min. The optimized FDs were characterized by saturation solubility study, drug content, in-vitro dissolution, fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, x-ray diffraction, (1)HNMR spectroscopy and pharmacodynamic evaluation. Capsules containing optimized FDs were prepared and compared with marketed brand (SIMVOTIN®). Finally, it can be concluded that the optimized FDs of SIM ameliorate the solubility and dissolution of drug with improved pharmacodynamic activity.

The highly conformal electrodeposition of a copolymer electrolyte (PMMA-PEO) into self-organized titania nanotubes (TiO2nt) is reported. The morphological analysis carried out by scanning electron microscopy and transmission electron microscopy evidenced the formation of a 3D nanostructure consisting of a copolymer-embedded TiO2nt. The thickness of the copolymer layer can be accurately controlled by monitoring the electropolymerization parameters. X-ray photoelectron spectroscopy measurements confirmed that bis(trifluoromethanesulfone)imide salt was successfully incorporated into the copolymer electrolyte during the deposition process. These results are crucial to fabricate a 3D Li-ion power source at the micrometer scale using TiO2nt as the negative electrode.

Graft polymerization of methoxy-poly(ethylene glycol) methacrylate, an ester of methacrylic acid and monomethoxy-poly(ethylene glycol) (PEO), was performed onto a polyetherurethane (PU) film and tube under different polymerization conditions by a plasma treatment technique. The surface of grafted PU film was characterized by staining with dye, x-ray photoelectron spectroscopy, contact angle, and zeta potential. All these measurements indicated that water-soluble chains were immobilized on the PU surface, their location being restricted to the film surface region. The PU surface showed reduced protein adsorption in vitro and reduced platelet adhesion in vitro and ex vivo. The optimum graft density suppressing the protein adsorption was as low as 5 micrograms cm(-2). When a small amount of dimethacrylate was added to the monomer solution for graft polymerization to introduce crosslinking in the grafted layer, protein adsorption was further slightly reduced. The extent of reduction in serum albumin adsorption was always less than that of gamma-globulin. Although platelet adhesion was largely reduced by the surface graft polymerization, a definite amount of protein was always adsorbed to the grafted surface.

Four different poly(ethylene oxide) [PEO] molecules were compared as grafted polymer layers for biomaterials' substrates: two linear polymers and two star polymers. Conditions maximizing surface coverage for each molecule were employed with the aim of inhibiting protein adsorption and increasing the density of end groups. Neutron reflectivities of the grafted layers immersed in deuterium oxide (heavy water) were measured and used to calculate volume fraction profiles of the polymer as a function of distance from the surface. These density profiles were combined with protein adsorption data on the grafted layers to compare with recent theoretical and experimental studies of protein resistance by PEO at surfaces. We found that the grafting density is maximized by coupling the linear PEO from a K2SO4 salt buffer, which is a poor solvent for PEO. However, the grafting density of star PEO was maximized when no K2SO4 was used and the stars were dissolved near the overlap concentration. Concentration profiles obtained from the reflectivity data show that the hydrated polymers swell to approximately 10 times the dried layer thickness and exhibit a low density (maximum volume fractions < 0.4 PEO) throughout the layer. The PEO surfaces obtained with both the star and linear polymers resisted adsorption of cytochrome-c and albumin except for a small amount of cytochrome-c adsorption on the short, many-armed star polymer surface. A hypothesis of adsorption on the star polymer layer is presented and criteria for controlling receptor-mediated cell-substrate interactions by ligand-modified chain ends are discussed.

This study was designed to evaluate the effect of polyethylene oxide (PEO) and negatively charged side chains on blood compatibility. For this, novel copolymers (MMA/MPEOMA/VSA copolymers) with both PEO and negatively chargeable side chains were synthesized by random copolymerization of methyl methacrylate (MMA), methoxy PEO monomethacrylate (MPEOMA; PEO mol wt 1000), and vinyl sulfonic acid sodium salt (VSA) monomers of different compositions. MMA/MPEOMA copolymer (with PEO side chains) and MMA/VSA copolymer (with negatively chargeable side groups) also were synthesized for purposes of comparison. The synthesized copolymers were characterized by 1H-nuclear magnetic resonance spectroscopy and gel permeation chromatography. They were coated onto polyurethane (PU) or polymethyl methacrylate (PMMA) films by spin coating. The surface properties of MMA/MPEOMA/VSA copolymers were compared by water contact angle and zeta potential with those of MMA/MPEOMA and MMA/VSA copolymers of similar MPEOMA or VSA composition. Using electron spectroscopy for chemical analysis and scanning electron microscopy, respectively, the behaviors of the adsorption of blood proteins (albumin, gamma-globulin, fibrinogen, and plasma proteins) and the adhesion of platelets on the copolymer-coated surfaces also were compared. Among the copolymers, the MMA/MPEOMA/VSA copolymer with a monomer molar ratio 8:1:1 was observed to be particularly effective in preventing both protein adsorption and platelet adhesion on the surfaces, probably owing to the combined effects of highly mobile, hydrophilic PEO side chains and negatively charged side groups in aqueous solution.

Like other colloidal particles bacteria have a surface charge that originates from the ionization of surface molecules and of the adsorption of ions from solution. Bacterial cell wall and membranes containing numerous proteins, lipid molecules, teichoic acids, lipopolisaccharides which give them characteristic charge. Therefore, bacterial cells undergo electrophoresis in a free solution with their own mobility depending on ionic strength and pH of buffer solution. Various electromigration techniques can be used to separate and determine the intact cells. Successful separation of five species of bacteria was obtained using a trimethylchlorosilane-modified capillary and a divinylbenzene-modified with suppressed EOF over a short distance (8.5 cm). The utilization of coated capillaries prevents adsorption of bacteria to the capillary wall. Another approach is utilization of a dilute dissolved polymer, polyethylene oxide (PEO) in the running buffer as a non-bonded coating for the purpose of altering the EOE These experiment have proved the possibility of diagnosing a variety of diseases and the ability to separate and identify viable cells.

Ni-doped TiO2 film catalysts were prepared by a plasma electrolytic oxidation (PEO) method and were mainly characterized by means of SEM, EDS, XRD, XPS, and DRS, respectively. The effects of Ni doping on the structure, composition and optical absorption property of the film catalysts were investigated along with their inherent relationships. The results show that the film catalyst is composed of anatase and rutile TiO2 with microporous structure. Doping Ni changes the phase composition and the lattice parameters (interplanar crystal spacing and cell volume) of the films. The optical absorption range of TiO2 film gradually expands and shifts to the red with increasing dosages. Both direct and indirect transition band gaps of the TiO2 films are deduced consequently. Moreover, the photocatalytic activity of the film catalysts for splitting Na2S+Na2SO3 solution into H2 is enhanced by doping with an appropriate amount of Ni. The as-prepared TiO2 film catalyst doping with 10 g/L of Ni(Ac)2 presents the highest photocatalytic reducing activity.

Calcification is a crucial step in the bone-bonding mechanism of PEO/PBT hydrogel copolymers (Polyactive, a new generation of bone-fillers. A beagle dog study was conducted to determine whether the preoperative presence of a calcium phosphate layer (precalcification) on a PEO/PBT 80/20 copolymer would further increase the bone-bonding rate. Standard bone cavities were filled with either precalcified or nonprecalcified porous cylindric PEO/PBT 80/20 implants, or hydroxyapatite granules held together with PEO/PBT 70/30, or were left unfilled. A significantly higher percentage of mineralized component was present in the cavities filled with the precalcified PEO/PBT 80/20 copolymer than in the control defects. As a result of swelling by fluid-uptake, the press-fit inserted copolymer implants showed a significant reduction in pore size, thus preventing optimal bone ingrowth. Both precalcification of the copolymer and underfilling of the defect, to create space for the copolymer to increase in diameter, stimulate postoperative calcification and bone ingrowth in PEO/PBT 80/20 copolymers.

Lecithin and hyaluronic acid were used for the preparation of polysaccharide decorated nanoparticles loaded with vitamin E using the cationic lipid dioctadecyldimethylammonium bromide (DODMA). Nanoparticles showed mean particle size in the range 130-350 nm and narrow size distribution. Vitamin E encapsulation efficiency was higher than 99%. These nanoparticles were incorporated in polymeric films containing Aloe vera extract, hyaluronic acid, sodium alginate, polyethyleneoxide (PEO) and polyvinylalcohol (PVA) as an innovative treatment in skin wounds. Films were thin, flexible, resistant and suitable for application on burn wounds. Additionally, in vitro occlusion study highlighted the dependence of the occlusive effect on the presence of nanoparticles. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of skin wounds, such as burns. The controlled release of the vitamin along with a reduction in water loss through damaged skin provided by the nanoparticle-loaded polymer film are considered important features for an improvement in wound healing and skin regeneration.

In this paper, we present a computational model of the adsorption and percolation mechanism of poloxamers (poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) triblock copolymers) across a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayer. A coarse-grained model was used to cope with the long time scale of the percolation process. The simulations have provided details of the interaction mechanism of Pluronics with lipid bilayer. In particular, the results have shown that polymer chains containing a PPO block with a length comparable to the DMPC bilayer thickness, such as P85, tends to percolate across the lipid bilayer. On the contrary, Pluronics with a shorter PPO chain, such as L64 and F38, insert partially into the membrane with the PPO block part while the PEO blocks remain in water on one side of the lipid bilayer. The percolation of the polymers into the lipid tail groups reduces the membrane thickness and increases the area per lipid. These effects are more evident for P85 than L64 or F38. Our findings are qualitatively in good agreement with published small-angle X-ray scattering experiments that have evidenced a thinning effect of Pluronics on the lipid bilayer as well as the role of the length of the PPO block on the permeation process of the polymer through the lipid bilayer. Our theoretical results complement the experimental data with a detailed structural and dynamic model of poloxamers at the interface and inside the lipid bilayer.

Pluronics are triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) with wide range of hydrophilic-lipophilic balance. In order to investigate the relationship between the chemical structures of Pluronics and the interfacial properties at the air-water interface by monolayer techniques, Pluronics L61, P65, F68, P84, P123, L35, and P105 were selected. Since cholesterol influenced substantially the molecular packing stage and the characteristics of cell membranes, the interactions between Pluronics and model cell membranes in the absence and presence of cholesterol were compared. The results of pi-A isotherms and surface elasticities of Pluronic monolayers indicated that the first and second transition like stage were mainly affected by the numbers of EO and PO monomers, respectively. Pluronics with higher hydrophobicities demonstrated larger surface activities and penetration abilities to dipalmitoylphosphatidylcholine (DPPC) monolayers, which might be due to hydrophobic interactions and van der Waals forces. In the presence of cholesterol, hydrogen bonding effects was supposed to exist between the 3beta-hydroxy group of cholesterol and ether oxygen of PEO chains, which led Pluronic F68, with the longest PEO chain herein, to exhibit significantly higher penetration ability. Our findings proposed a theoretical basis for selection of optimized drug carriers and the starting point for further investigations.

The pore variations of ordered cage-type mesoporous silica FDU-12s have been analyzed in detail by PXRD, SAXS, nitrogen sorption, and electron crystallography. FDU-12s with a cubic symmetry (space group, Fmm) were templated by amphiphilic triblock copolymer F127 with the addition of 1,3,5-trimethylbenzene and KCl under an acidic condition. Three typical samples with different unit cell sizes, pore cage diameters, and entrance sizes were obtained from different synthesis and hydrothermal treatment temperatures, as indicated by the differences in the PXRD and SAXS patterns. The pore structure changes in the three materials were observed by nitrogen adsorption/desorption and 3-D reconstruction of HRTEM images taken from different crystal orientations. The approximate pore structures of FDU-12s can be regarded as a face-centered cubic (fcc) close-packing of spherical cages, each connected to 12 nearest neighboring cages. However, the ideal spherical model is only valid for the FDU-12s prepared at a low temperature (L-FDU-12-100). The cage shape of the FDU-12s synthesized at a high temperature deviates from perfect spheres and is accompanied by an entrance enlargement. The temperature-dependent behavior of the PEO block is discussed with regard to its influence on the micelles and hence the cage configuration. The better understanding of the formation mechanism via the combined characterization techniques and modeling may lead to a more rational approach for tuning the pore cages and entrances of the mesoporous FDU-12 materials.

Motivated by the deficiencies of the previous MARTINI models of poly(ethylene oxide) (PEO), we present a new model featuring a high degree of transferability. The model is parametrized on (a) a set of 8 free energies of transfer of dimethoxyethane (PEO dimer) from water to solvents of varying polarity; (b) the radius of gyration in water at high dilution; and (c) matching angle and dihedral distributions from atomistic simulations. We demonstrate that our model behaves well in five different areas of application: (1) it produces accurate densities and phase behavior or small PEO oligomers and water mixtures; (2) it yields chain dimensions in good agreement with the experiment in three different solvents (water, diglyme, and benzene) over a broad range of molecular weights (∼1.2 kg/mol to 21 kg/mol); (3) it reproduces qualitatively the structural features of lipid bilayers containing PEGylated lipids in the brush and mushroom regime; (4) it is able to reproduce the phase behavior of several PEO-based nonionic surfactants in water; and (5) it can be combined with the existing MARTINI PS to model PS-PEO block copolymers. Overall, the new PEO model outperforms previous models and features a high degree of transferability.

In recent years, calcium phosphate-base composites, such as hydroxyapatite (HA) and carbonate apatite (CA) have been considered desirable and biocompatible coating layers in clinical and biomedical applications such as implants because of the high resistance of the composites. This review focuses on the effects of voltage, time and electrolytes on a calcium phosphate-base composite layer in case of pure titanium and other biomedical grade titanium alloys via the plasma electrolytic oxidation (PEO) method. Remarkably, these parameters changed the structure, morphology, pH, thickness and crystallinity of the obtained coating for various engineering and biomedical applications. Hence, the structured layer caused improvement of the biocompatibility, corrosion resistance and assignment of extra benefits for Osseo integration. The fabricated layer with a thickness range of 10 to 20 μm was evaluated for physical, chemical, mechanical and tribological characteristics via XRD, FESEM, EDS, EIS and corrosion analysis respectively, to determine the effects of the applied parameters and various electrolytes on morphology and phase transition. Moreover, it was observed that during PEO, the concentration of calcium, phosphor and titanium shifts upward, which leads to an enhanced bioactivity by altering the thickness. The results confirm that the crystallinity, thickness and contents of composite layer can be changed by applying thermal treatments. The corrosion behavior was investigated via the potentiodynamic polarization test in a body-simulated environment. Here, the optimum corrosion resistance was obtained for the coating process condition at 500 V for 15 min in Ringer solution. This review has been summarized, aiming at the further development of PEO by producing more adequate titanium-base implants along with desired mechanical and biomedical features.

The combination of capillary electrophoresis (CE) and light-emitting diode-induced fluorescence (LED-IF) detection has been demonstrated in the analysis of major amino acids in tea leaves and beverages. The separation efficiency of amino acids, which were derivatized with naphthalene-2,3-dicarboxaldehyde (NDA), depended on the capillary length and PEO concentration. We suggested that the interactions between the NDA derivatives and poly(ethylene oxide) (PEO) molecules are based on hydrogen bonding, hydrophobic patches, and Van der Waals forces. The magnitude of EOF and the interactions between them can be further controlled by the capillary length. The separation of 17 NDA-amino acids derivatives was completed within 16min using 0.5% PEO and 60cm capillary length. The relative standard deviations (R.S.D.) of their migration times (n=5) were less than 2.7%. Additionally, the limits of detection at signal-to-noise ratio 3 for the tested amino acids ranged from 3.6 to 28.3nM. Quantitative determination of amino acids in tea leaves and beverages was accomplished by our proposed method. This study showed that amino acid present in highest concentration in tea leaves and beverages is gamma-aminobutyric acid and theanine, respectively. The experimental results suggest that our proposed methods have great potential in the investigation of the biofunction of different tea samples.

Iodine deficiency is a public health problem that is easily prevented in many countries through having a salt iodization program. However, the World Health Organization (WHO) recommends that particular population groups including infants and young children have a sufficient level of daily iodine intake, while also reducing salt consumption in their diet. While many iodine supplements are available, swallowing tablet supplements is physically difficult for young children; thus, there is a need for the development of novel iodine delivery systems for pediatric patients. In this study a novel, ultrarapidly dissolving, nanofiber-based orodispersible film formulation containing iodine which is constructed from nanofibers was manufactured using an electrospinning technique. The potassium iodate (KIO3)-loaded poly(ethylene oxide) (PEO) fiber orodispersible films dissolve within seconds on wetting (applying on the tongue) without the need for the consumption of water. The electrospinning process and KIO3 loading did not alter the crystallinity and conformation of PEO. With high loading, KIO3 nanocrystals are present in the fibers. This formulation design allows easy administration of iodine for preventing childhood iodine deficiency. We have also described a novel and easy method for producing and harvesting nanocrystals of inorganic salts that can be potentially adopted for use in other relevant fields.

Sulfonated poly(ethylene oxide) (PEO)-grafted polyurethane (PU) (PU-PEO-SO(3)) prepared by bulk modification was used to coat both PU heart valves and vascular grafts, and their in vivo biocompatibility was evaluated using a canine shunt method. The two devices were implanted for up to 39 days and retrieved at specific time points for the analysis of blood compatibility, biostability, and calcium deposition. When the surface of the retrieved specimens was examined using scanning electron microscopy, platelet adhesion and thrombus formation appeared to be significantly lesser formed on the PU-PEO-SO(3)-coated implants, compared with the untreated PUs. While molecular weights of untreated PUs were found by gel permeation chromatography to be decreased after 39 days from implantation, the same remained barely changed with the PU-PEO-SO(3)-coated ones. The inductively coupled plasma study indicated that the amount of deposited calcium was significantly reduced in the surface-modified PU implants. The efficacy of PU-PEO-SO(3)-coated implants in terms of blood compatibility, biostability, and calcification resistance may render them as a promising biomedical material in the application for blood/tissue-contacting tissues and organs.

This study aimed to improve bone regeneration using a timed-release system for periosteal expansion osteogenesis (TIME-PEO) using a shape memory alloy (SMA) mesh device and absorbable thread in a rabbit model.

METHODS

Twelve rabbits were used in this study. The device was inserted under the periosteum at the forehead, then pushed, bent, and attached to the bone surface and fixed with an absorbable thread. Rabbits were divided into groups C1 (5 weeks postoperatively without dynamic elevation), C2 (8 weeks postoperatively without dynamic elevation), T1 (5 weeks postoperatively from TIME-PEO), and T2 (8 weeks postoperatively from TIME-PEO). Newly formed bone was evaluated histologically and radiographically.

RESULTS

The newly formed bone volume to elevated bone volume ratio was 6.1% in C1, 21.9% in T1 15.5% in C2 and 36.0% in T2. These quantitative data indicate that TIME-PEO group had a significantly higher volume than that of the control group (P < 0.05). Histologically, multiple dome-shaped bones, outlined by thin and scattered trabeculae, over the original bone surface were evident in the T group.

CONCLUSIONS

This technique appears to be a promising clinical alternative for alveolar bone augmentation and introduces the new concept of "dynamic guided bone regeneration" for atrophic alveolar bone.

The incidence of the structural features on the self-assembly of different poloxamines (the conventional sequential Tetronic 304, 901, 904, 908, 1107, 1301, and 1307; a reverse-sequential counterpart Tetronic 150R1; and a chemically modified derivative, N-methylated Tetronic 1107) was thoroughly studied in 10 mM HCl by means of pi-A isotherm, surface tension, and pyrene fluorescence measurements. The size and size distribution of the aggregates were investigated by dynamic and static light scattering, and the morphology was probed by transmission electron microscopy. The abilities of the different derivatives to solubilize the drug simvastatin were also evaluated. Poloxamines with both higher PO/EO ratio and molecular weight (T1301 and T150R1) led to micelles with larger and more hydrophobic cores, particularly adequate for hosting hydrophobic molecules and protecting the labile lactone form of simvastatin from hydrolysis. On the other hand, the hydroxy acid form of simvastatin interacted with the central ethylenediamine group under alkaline pH (T304) or when a permanent positive charge due to methylation was present. Micelles of long poloxamine molecules containing large PPO blocks (with 23-29 units, namely, T1301, T1307, and T150R1), particularly the one that also has long PEO blocks, were the most physically stable toward dilution.

In the design of parenteral delivery systems the modulation of the biodegradation of a polymer matrix represents a promising strategy to control drug release. We have investigated the degradation of ABA triblock copolymers, consisting of poly(lactide-co-glycolide) A-blocks and poly(oxyethylene) B-blocks, and PLG, poly(lactide-co-glycolide), with respect to swelling behaviour, molecular weight loss and polymer erosion. Implants were prepared by either compression moulding or extrusion using a laboratory ram extruder. Insertion of an elastoplastic B-block did not lower the processing temperature, but the entanglement of the polymer chains was significantly reduced as can be seen from the diameters of the extruded rods. The swelling of the rods showed a volume extension of 130% for an ABA containing 50% PEO and 20% for an ABA containing 20% PEO. Using 1H-NMR it was found that protons in the B-blocks of the swollen ABA copolymers were mobile, while the A-blocks remained rigid during incubation. The analysis of the pH inside ABA rods using electron paramagnetic resonance, EPR, gave a pH of 5.2 after incubation with a subsequent increase to pH 6.0 during the first day, approaching the pH of the medium after nearly 33 d. Acidic degradation products did not accumulate inside the ABA rods. Degradation and erosion started immediately upon incubation. By contrast, PLG rods showed the typical profile of degradation and erosion. In this case, the influence of the geometry of the device was insignificant. Consequently, ABA triblock copolymers may widen the spectrum of parenteral drug delivery with regard to release of pH-sensitive drugs as well as erosion-controlled release kinetics.

Nasal administration of plasmid DNA is emerging as a new route of delivery for therapeutic genes and DNA vaccines. To improve the intranasal absorption of plasmid DNA, we designed delivery systems composed of in situ gelling and mucoadhesive polymers. Poloxamers (Pol) were used to provide in situ gelling property. Polycarbophil (PC) or polyethylene oxide (PEO) was used as mucoadhesive polymers. The gelation temperatures of the formulations slightly decreased by the mucoadhesive polymers, but not by plasmid DNA. The in vitro release of plasmid DNA from the gels followed Fickian diffusion. The absorption of plasmid DNA varied with the contents and type of mucoadhesive polymers. Of vehicles, Pol/PC 0.2% showed the highest absorption with an area under the curve value 11-fold higher than saline, the conventional vehicle. The nasal retention of plasmid DNA was highly prolonged by mucoadhesive polymers. At 3 h postdose, the nasal tissue levels of plasmid DNA given in Pol/PC and Pol/PEO 0.8% were 10- and 40-fold higher relative to saline. The histopathology of nasal tissues was not altered after repeated dosing over 2 weeks. The mRNA expression of plasmid DNA delivered by Pol or Pol/PEO 0.4% was observed in the nasal tissues. These results indicate that the nasal absorption of plasmid DNA can be effectively and safely enhanced by using in situ gelling and mucoadhesive polymer-based vehicles.

The objectives of the present research investigations were to (i) elucidate the mechanism for the oxidative degradation of Delta(9)-tetrahydrocannabinol (THC) in polymer matrix systems prepared by a hot-melt fabrication procedure, and (ii) study the potential for controlling these mechanisms to reduce the degradation of THC in solid dosage formulations. Various factors considered and applied included drug-excipient compatibility, use of antioxidants, cross-linking in polymeric matrices, microenvironment pH, and moisture effect. Instability of THC in polyethylene oxide (PEO)-vitamin E succinate (VES) patches was determined to be due to chemical interaction between the drug and the vitamin as well as with the atmospheric oxygen. Of the different classes and mechanisms of antioxidants studied, quenching of oxygen by reducing agents, namely, ascorbic acid was the most effective in stabilizing THC in PEO-VES matrices. Only 5.8% of the drug degraded in the ascorbic acid-containing patch as compared to the control (31.6%) after 2 months of storage at 40 degrees C. This coupled with the cross-linking extent and adjustment of the pH microenvironment, which seemed to have an impact on the THC degradation, might be effectively utilized towards stabilization of the drug in these polymeric matrices and other pharmaceutical dosage forms. These studies are relevant to the development of a stable transmucosal matrix system for the therapeutic delivery of amorphous THC.