Synthesis and electrostatic nano-assembly of water-soluble polybenzothiadiazole derivatives with long-wavelength emission in the solid states.

We have synthesized APBT and APTBT containing benzothiadiazole units by Suzuki cross-coupling reaction with good yield. The polymers showed blue emission colors in aqueous solutions, while long wavelength shift was observed in the solid state due to facilitated exciton migration. APBT and APTBT are water-soluble and highly-fluorescent conjugated polymers with negatively charged sulfonate side chains and thus they can be electrostatically assembled with oppositely charged polyelectrolyte such as cationic polymer, poly(dimethyldiallylammonium chloride) (PDAC) via layer-by-layer (LbL) deposition technique on a glass slide. According to the increased the number of bilayer, we found that the assembled film exhibited larger enhancement of the long wavelength emission relative to the blue emission, due to the increased excition migration.

Gentamicin-loaded wound dressing with polyvinyl alcohol/dextran hydrogel: gel characterization and in vivo healing evaluation.

To develop a gentamicin-loaded wound dressing, cross-linked hydrogel films were prepared with polyvinyl alcohol (PVA) and dextran using the freezing-thawing method. Their gel properties such as gel fraction, swelling, water vapor transmission test, morphology, tensile strength, and thermal property were investigated. In vitro protein adsorption test, in vivo wound healing test, and histopathology were performed. Dextran decreased the gel fraction, maximum strength, and thermal stability of hydrogels. However, it increased the swelling ability, water vapor transmission rate, elasticity, porosity, and protein adsorption. The drug gave a little positive effect on the gel properties of hydrogels. The gentamicin-loaded wound dressing composed of 2.5% PVA, 1.13% dextran, and 0.1% drug was more swellable, flexible, and elastic than that with only PVA because of its cross-linking interaction with PVA. In particular, it could provide an adequate level of moisture and build up the exudates on the wound area. From the in vivo wound healing and histological results, this gentamicin-loaded wound dressing enhanced the healing effect more compared to conventional product because of the potential healing effect of gentamicin. Thus, this gentamicin-loaded wound dressing would be used as a potential wound dressing with excellent forming and improved healing effect in wound care.

Development of polyvinyl alcohol-sodium alginate gel-matrix-based wound dressing system containing nitrofurazone.

Polyvinyl alcohol (PVA)/sodium alginate (SA) hydrogel matrix-based wound dressing systems containing nitrofurazone (NFZ), a topical anti-infective drug, were developed using freeze-thawing method. Aqueous solutions of nitrofurazone and PVA/SA mixtures in different weight ratios were mixed homogeneously, placed in petri dishes, freezed at -20 degrees C for 18h and thawed at room temperature for 6h, for three consecutive cycles, and evaluated for swelling ratio, tensile strength, elongation and thermal stability of the hydrogel. Furthermore, the drug release from this nitrofurazone-loaded hydrogel, in vitro protein adsorption test and in vivo wound healing observations in rats were performed. Increased SA concentration decreased the gelation%, maximum strength and break elongation, but it resulted into an increment in the swelling ability, elasticity and thermal stability of hydrogel film. However, SA had insignificant effect on the release of nitrofurazone. The amounts of proteins adsorbed on hydrogel were increased with increasing sodium alginate ratio, indicating the reduced blood compatibility. In vivo experiments showed that this hydrogel improved the healing rate of artificial wounds in rats. Thus, PVA/SA hydrogel matrix based wound dressing systems containing nitrofurazone could be a novel approach in wound care.

Preparation and lead ion removal property of hydroxyapatite/polyacrylamide composite hydrogels.

We report the synthesis of hydroxyapatite/polyacrylamide (HAp/PAAm) composite hydrogels with various HAp contents by free radical polymerization and their removal capability of Pb(2+) ions in aqueous solutions with controlled initial Pb(2+) ion concentrations and pH values of 2-5. The swelling ratio of the composite gels in aqueous solutions decreases with increasing the HAp content in the gels. The composite gel with higher HAp content exhibits the higher removal capacity of Pb(2+) ions owing to the higher adsorption sites for Pb(2+) ions, but shows the slower removal rate of Pb(2+) ions due to the lower degree of swelling. The removal mechanism of Pb(2+) ion is very sensitive to the pH value in aqueous solution, although the removed amount of Pb(2+) ion is nearly same, regardless of pH values of 2-5. The removal mechanism, the dissolution of HAp in the composite gel and subsequent precipitation of hydroxypyromorphite (HPy), is dominant at lower pH 2-3, whereas the mechanism, the adsorption of Pb(2+) ions on the composite gel and following cation exchange reaction between Pb(2+) ions adsorbed and Ca(2+) of HAp, is dominant at higher pH 4-5. The equilibrium removal process of Pb(2+) ions by the composite gels at pH 5 is described well with the Langmuir isotherm model. The equilibrium removal capacities of the composite gels with 30, 50, and 70 wt.% HAp contents are evaluated to be 123, 178, and 209 mg/g, respectively.

Removal of lead ions in aqueous solution by hydroxyapatite/polyurethane composite foams.

We have prepared hydroxyapatite/polyurehthane (HAp/PU) composite foams with two different HAp contents of 20 and 50 wt.% and investigated their removal capability of Pb2+ ions from aqueous solutions with various initial Pb2+ ion concentrations and pH values of 2-6. HAp/PU composite foams synthesized exhibited well-developed open pore structures which provide paths for the aqueous solution and adsorption sites for Pb2+ ions. With increasing the HAp content in the composites, the removal capability of Pb2+ ions by the composite foams increases owing to the higher adsorption capacity, whereas the removal rate is slower due to the less uniform dispersity of HAp in composite foams. The removal rate of Pb2+ ions is also slower with increasing the initial Pb2+ ion concentration in aqueous solutions. The removal mechanism of Pb2+ ion by the composites is varied, depending on the pH value of aqueous solution: the dissolution of HAp and precipitation of hydroypyromorphite is dominant at lower pH 2-3, the adsorption of Pb2+ ions on the HAp/PU composite surface and ion exchange reaction between Ca2+ of HAp and Pb2+ in aqueous solution is dominant at higher pH 5-6, and two removal mechanisms compete at pH 4. The equilibrium removal process of Pb2+ ions by the HAp/PU composite foam at pH 5 was described well with the Langmuir isotherm model, resulting in the maximum adsorption capacity of 150 mg/g for the composite foam with 50 wt.% HAp content.

Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188.

Ibuprofen-Poloxamer 188 (P 188) binary solid dispersions (SD) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility, in vitro release, and oral bioavailability of ibuprofen in rats. Loss of their individual surface properties during melting and solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of its interactions with P 188. However, no such interactions in the solid state were confirmed by FTIR spectra which showed the presence of drug crystalline in SDs. Immediate and complete release of ibuprofen from SDs might be because of the reduction in the drug crystalline due to eutectic formation, and their dosing to fasted rats resulted in a significant increase in the area under curve (AUC) of the plasma concentration versus time curve and the maximum plasma concentration (Cmax), and a significant decrease in the time to reach Cmax (Tmax) over ibuprofen and physical mixtures.

An experimental study for syndiotactic polyvinyl alcohol spheres as an embolic agent: can it maintain spherical shape in vivo?

Syndiotactic polyvinyl alcohol (PVA) had been developed to overcome the drawbacks of atactic PVA spheres that deform easily, which can lead to non-target embolization. This study was performed to evaluate the in vivo stability of spherical shape of the syndiotactic PVA spheres. Selective arteriography and transarterial embolization (TAE) were performed in the main renal arteries of eight New Zealand white rabbits using syndiotactic PVA sphere that consisted of syndiotactic PVA skin and a copolymer core of vinyl acetate/vinyl pivalate. The size of the syndiotactic PVA spheres used for the TAE was 212-355 µm. The rabbits were sacrificed 12-14 days after TAE. Gross and microscopic examinations of each kidney were performed. The microscopic examination showed infarction of all embolized kidneys. Syndiotactic PVA spheres were seen uniformly within the arterial lumen and appeared as round ring-like structures without any deformity. The syndiotactic PVA spheres exclusively occupied the arterial lumen. As a conclusion, syndiotactic PVA spheres maintained their spherical shape without significant deformation in this in vivo short-term experimental study. Further investigation is necessary for evaluation of detailed effects of physical stability in tumor embolization.

Superhydrophobic PLA fabrics prepared by UV photo-grafting of hydrophobic silica particles possessing vinyl groups.

Superhydrophobic poly(lactic acid) (PLA) fabrics are prepared by UV photo-grafting of hydrophobic silica particles possessing vinyl functional groups on the surfaces, which is a novel one-step process to provide surface with roughness as well as hydrophobicity simultaneously. For this purpose, hydrophobic silica particles with vinyl groups and average diameter of 1.51+/-0.05 microm are synthesized via a sol-gel process. The silica particles possessing vinyl groups are found to be effectively immobilized on PLA fabrics via UV photo-grafting reaction. The water contact angle of the treated PLA fabric is measured to be approximately 150 degrees, which is high enough to exhibit the Lotus effect as a result of the superhydrophobicity.

Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan.

The purpose of this study was to develop a minocycline-loaded wound dressing with an enhanced healing effect. The cross-linked hydrogel films were prepared with polyvinyl alcohol (PVA) and chitosan using the freeze-thawing method. Their gel properties, in vitro protein adsorption, release, in vivo wound healing effect and histopathology were then evaluated. Chitosan decreased the gel fraction, maximum strength and thermal stability of PVA hydrogel, while it increased the swelling ability, water vapour transmission rate, elasticity and porosity of PVA hydrogel. Incorporation of minocycline (0.25%) did not affect the gel properties, and chitosan hardly affected drug release and protein adsorption. Furthermore, the minocycline-loaded wound dressing composed of 5% PVA, 0.75% chitosan and 0.25% drug was more swellable, flexible and elastic than PVA alone because of relatively weak cross-linking interaction of chitosan with PVA. In wound healing test, this minocycline-loaded PVA-chitosan hydrogel showed faster healing of the wound made in rat dorsum than the conventional product or the control (sterile gauze) due to antifungal activity of chitosan. In particular, from the histological examination, the healing effect of minocycline-loaded hydrogel was greater than that of the drug-loaded hydrogel, indicating the potential healing effect of minocycline. Thus, the minocycline-loaded wound dressing composed of 5% PVA, 0.75% chitosan and 0.25% drug is a potential wound dressing with excellent forming and enhanced wound healing.

Preparation and evaluation of fast dissolving ibuprofen-polyethylene glycol 6000 solid dispersions.

To improve its oral absorption, rapidly dissolving ibuprofen solid dispersions (SD) were prepared in a relatively easy, simple, quick, inexpensive, and reproducible manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). They were evaluated for solubility, in vitro release, and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and resolidification as revealed by SEM indicated the formation of effective SDs. Absence or shifting toward the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. However, no such interactions in the solid state were confirmed by FTIR spectra that showed the presence of drug crystalline in SDs. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C(max), and a significant decrease in T(max) over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast-dissolving ibuprofen SDs by low temperature melting method using PEG 6000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution, and absorption rate of ibuprofen.

Development of clindamycin-loaded wound dressing with polyvinyl alcohol and sodium alginate.

To develop a clindamycin-loaded wound dressing, cross-linked hydrogel films were prepared using freeze-thawing method with various mixtures of polyvinyl alcohol (PVA) and sodium alginate (SA). The physicochemical properties such as swelling ratio, tensile strength and elongation of hydrogels were evaluated. The drug release from this clindamycin-loaded hydrogel, in vitro protein adsorption test and in vivo wound healing observations in rats were then performed. Increased SA concentration decreased the gelation %, maximum strength and break elongation, but it resulted into an increment in the swelling ability, elasticity and thermal stability of hydrogel film. However, SA had insignificant effect on the release of clindamycin. This hydrogel improved the healing rate of artificial wounds in rats. Thus, a clindamycin-loaded wound dressing with PVA and SA hydrogel should be a candidate for wound care.

Enhanced oral bioavailability of piroxicam in rats by hyaluronate microspheres.

To enhance the dissolution and oral bioavailability of poorly water soluble piroxicam, the piroxicam-loaded hyaluronic microspheres were prepared with various ratios of piroxicam, sodium hyaluronate and polyethylene glycol 4000 (PEG) using a spray dryer, and their physicochemical properties such as shape, size, drug-loading efficiency and dissolution were investigated. The pharmacokinetic study of piroxicam-loaded hyaluronic micropheres in rats was then performed compared to piroxicam powder. The piroxicam-loaded hyaluronic microspheres, spherical in shape, had the geometric mean diameters of about 1.5 microm and drug loading efficiency of about 90%, irrespective of ratio of piroxicam/sodium hyaluronate/PEG. The hyaluronic microspheres containing PEG gave significantly higher dissolution rates of drug than did piroxicam powder, PEG-based solid dispersion system and hyaluronic microspheres without PEG, suggesting that the hyaluronic microsphere with sodium hyaluronate and PEG was more useful for improving the dissolution rate of poorly water soluble piroxicam. The piroxicam-loaded hyaluronic microcapsule composed of (piroxicam/sodium hyaluronate/PEG; 2: 20: 1) gave about threefold improved dissolution of drug in water for 4 h compared to piroxicam powder. It showed higher plasma concentrations of drug compared to piroxicam powder. It gave significantly higher AUC and faster Tmax of piroxicam than did piroxicam powder. In particular, the AUC of piroxicam from hyaluronic microsphere was about twofold higher than that from piroxicam powder, suggesting that it could enhance the oral bioavailability of piroxicam. Thus, the hyaluronic microsphere developed using spray-drying technique with sodium hyaluronate and PEG was a more effective oral dosage form for poorly water soluble piroxicam.

Preparation, characterization and evaluation of coenzyme Q10 binary solid dispersions for enhanced solubility and dissolution.

Phase solubility behavior of coenzyme Q10 (CoQ10) at 25 degrees C in various molar solutions of poloxamer 188 (P188) in water was observed and their binary solid dispersions (BSD) at different weight ratios were prepared by a simple, rapid, cost effective, uncomplicated and potentially scalable low temperature melting method. BSDs were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC), and evaluated for improved solubility at 25 degrees C and 37 degrees C and in-vitro release of CoQ10 at 37 degrees C in distilled water. Solubility of CoQ10 increased with increasing concentrations of P188 in water. Gibbs free energy (deltaG(o)tr) values were all negative indicating the spontaneous nature of CoQ10 solubilization and decreased with increasing concentration of P188 demonstrating that the reaction conditions became more favorable as the concentration of P188 increased. DSC and SEM analysis indicated that the homogeneity of dispersion was not at the molecular level. However, BSDs exhibited a remarkably improved aqueous solubility and dissolution of CoQ10.

Enhanced oral bioavailability of ibuprofen in rats by poloxamer gel using poloxamer 188 and menthol.

To improve the oral bioavailability of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the ibuprofen-loaded preparations composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed an abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/mL. The simultaneous addition of menthol and poloxamer 188 significantly improved the dissolution rates of ibuprofen from aqueous solution due to the ibuprofen solubility-improving effect of menthol in the presence of poloxamer. Furthermore, the ibuprofen-loaded preparation with menthol and poloxamer 188 gave significantly higher initial plasma concentrations, Cmax, and AUC of ibuprofen than did the preparation without menthol and poloxamer 188, indicating that the simultaneous addition of menthol and poloxamer 188 could improve the oral bioavailability of ibuprofen in rats. In modern pain management it is always desirable for the ibuprofen-loaded preparation with poloxamer 188 and menthol to show a rapid onset of action with a minimal phase of lag time to feel the decreased pain. From an industry point of view, it is more desirable for a formulation to be fast acting, easy to use, and cost effective. Thus, the ibuprofen-loaded preparation with poloxamer 188 and menthol was a more effective oral dosage form for poorly water-soluble ibuprofen.