Influence of Mass Ratio of Polyols on Properties of Polycaprolactone-Polyethylene Glycol/Methylene Diphenyl Diisocyanate/Diethylene Glycol Hydrogels

Polyurethane (PU) hydrogels with good hydrophilicity and biocompatibility have been applied as biomedical materials. A series of polyurethane prepolymers based on methylene diphenyl diisocyanate (MDI), polycaprolactone (PCL) and polyethylene glycol (PEG), using diethylene glycol (DEG) as the chain-extender, were synthesized; then the polyurethane hydrogels were obtained from the prepolymers using benzoyl peroxide (BPO) as a cross-linker by free radical polymerization. The influences of the ratio of polyols (PCL and PEG) on the contact angle, swelling ratio and morphology of the polyurethane hydrogel were investigated. The loading capacity and release behavior of chloramphenicol from the PCL-PEG/MDI/DEG hydrogels with different compositions were also studied. The contact angle and swelling degree results showed that the PCL-PEG/MDI/DEG hydrogel with PCL/PEG mass ratio of 3:1 had higher hydrophilicity than that with PCL/PEG mass ratios of 1:1 and 1:3. All PCL-PEG/MDI/DEG hydrogels showed three dimensional porous structures; however, the pore size increased with increasing PEG content. The chloramphenicol release kinetics from PCL-PEG/MDI/DEG hydrogels indicated Fickian diffusion, and the drug release rate increased with increasing PEG content in the PU hydrogels.     

Preparation and Properties of Polyurethane Hydrogels Based on Methylene Diphenyl Diisocyanate/Polycaprolactone-Polyethylene Glycol

Polyurethane (PU) hydrogel is an important biomedical material for drug controlled release systems, wound dressings and medical bandages. Three series of polyurethane prepolymers based on methylene diphenyl diisocyanate (MDI), polycaprolactone (PCL) and polyethylene glycol (PEG), using diethylene glycol (DEG), N-methyldiethanolamine (MDEA) or dimethylolpropionic acid (DMPA), as the chain-extender, were prepared. Then the polyurethane hydrogels were obtained from the prepolymers, using benzoyl peroxide (BPO) as a cross-linking agent, by free radical polymerization. The influences of the types of chain-extenders and polyols on the contact angle, swelling ratio and morphology of the polyurethane hydrogels were investigated. The effect of the variety of the chain-extenders in the PU hydrogel on the drug release behavior was also studied. The FT-IR results showed that the PU hydrogels were successfully synthesized. The introduction of PEG improved the hydrophilicity of the PU hydrogels. The MDI/PCL-PEG/DEG hydrogel was hydrophobic, and there were small micropores on its surface; while the MDI/PCL-PEG/DMPA and MDI/PCL-PEG/MDEA hydrogels had high hydrophilicity and a micropouous structure on their surface due to the existence of carboxyl and tertiary amino functional groups. The change of chain-extenders had no significant effect on the cumulative drug release of chloramphenicol from the PU hydrogels. However, the introduction of PEG increased the drug release rate. The chloramphenicol release kinetics from the MDI/PCL-PEG hydrogels indicated non-Fickian diffusion.     

The Effect of Benzoyl Peroxide and Divinyl Benzene on the Properties of Cross-Linked Recycled Polyolefin Blends

The effect of peroxide cross-linking on the properties and morphology of recycled polyethylene (PE)/polypropylene (PP) blends was characterized. The addition of benzoyl peroxide (BPO) decreased the melt flow rate (MFR) and increased the impact strength of the recycled polymer blends. Divinyl benzene (DVB) is often used as a cross-linking agent assistant. Compared with BPO modification, the addition of BPO together with DVB improved the cross-linking efficiency and further increased the impact strength of the recycled polymer blends. The effect of BPO content on the MFR and the mechanical properties was also studied with the DVB content fixed. However, chemical cross-linking slightly reduced the thermal stability of the polymer blends. The morphology of the modified and unmodified polymer blends showed that with the addition of BPO, with or without DVB, the compatibility of the PE/PP blends was improved, resulting in enhanced impact strength.     

Synthesis and Characterization of Methylacrylic Acid and Butyl Acrylate Grafted onto Ethylene-Propylene-Diene Terpolymer

A multi-component polymer of methacrylic acid (MAA) and butyl acrylate (BA) grafted onto ethylene-propylene-diene (EPDM) terpolymer was synthesized in toluene using benzoyl peroxide (BPO) as initiator. The effect of EPDM/MAA-BA ratio and MAA/BA ratio on the grafting ratio of polymerization was investigated. The products were characterized by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), surface energy, inherent viscosity, and atomic force microscopy (AFM). The results showed that the MAA and BA monomers were successfully grafted onto EPDM. Furthermore, after being grafted, the polarity of the surface of the EPDM-g-MAA-BA increased with increasing grafting ratio, and the morphology of its surface became more smooth.     

Electrodeposited metals at conducting polymer electrodes: I—Effect of particle size and film thickness on electrochemical response

Conducting polymers are electrochemically polymerized at platinum electrode substrates. The thickness, porosity and surface morphology of the resulting films are controlled by the charge passing during electropolymerization step and the synthesis conditions. The polymer films are modified by electrochemically depositing platinum particles. The technique of deposition depends on applying a programmed potential pulse at the polymer film from a solution containing platinum complex that resulted in the formation of platinum particles of controlled size and distribution. The effect of changing the size of platinum particles and polymer film thickness on the voltammetric behavior of the resulting hybrid material showed noticeable changes in the electro-catalytic current in acid medium. On the other hand, the electrochemical impedance spectroscopy experiments showed that diffusion and charge-transfer rate increased in the order: unmodified polymer films, thin polymer films containing small size/amount of platinum particles and relatively thick polymer films containing larger size/amount of platinum particles. The morphology of polymer films, size and distribution of platinum particles in the film were studied by scanning electron microscopy. The presence of platinum and its distribution over the film surface was confirmed from the X-ray dispersive analysis and surface mapping. The hybrid materials are good candidates for the application in devices for exchange of hydrogen ions.     

In vitro studies of cutaneous retention of magnetic nanoemulsion loaded with zinc phthalocyanine for synergic use in skin cancer treatment

In this study was developed a new nano drug delivery system (NDDS) based on association of biodegradable surfactants with biocompatible magnetic fluid of maguemita citrate derivative. This formulation consists in a magnetic emulsion with nanostructured colloidal particles. Preliminary in vitro experiments showed that the formulation presents a great potential for synergic application in the topical release of photosensitizer drug (PS) and excellent target tissue properties in the photodynamic therapy (PDT) combined with hyperthermia (HPT) protocols. The physical chemistry characterization and in vitro assays were carried out by Zn(II) Phtalocyanine (ZnPc) photosensitizer incorporated into NDDS in the absence and the presence of magnetic fluid, showed good results and high biocompatibility. In vitro experiments were accomplished by tape-stripping protocols for quantification of drug association with different skin tissue layers. This technique is a classical method for analyses of drug release in stratum corneum and epidermis+dermis skin layers. The NDDS formulations were applied directly in pig skin (tissue model) fixed in the cell's Franz device with receptor medium container with a PBS/EtOH 20% solution (10 mM, pH 7.4) at 37 °C. After 12 h of topical administration stratum corneum was removed from fifty tapes and the ZnPc retained was evaluated by solvent extraction in dimetil-sulphoxide under ultrasonic bath. These results indicated that magnetic nanoemulsion (MNE) increase the drug release on the deeper skin layers when compared with classical formulation in the absence of magnetic particles. This could be related with the increase of biocompatibility of NDDS due to the great affinity for the polar extracelullar matrix in the skin and also for the increase in the drug partition inside of corneocites wall.     

Preparation and Properties of Polyurethane Hydrogels Based on Hexamethylene Diisocyanate/Polycaprolactone-Polyethylene Glycol

Hydrogels are considered an optimum material for controlled release drug systems and tissue engineering scaffolds since they are tri-dimensional networks. In this work hexamethylene diisocyanate (HMDI), polycaprolactone (PCL) and polyethylene glycol (PEG) were used to prepare polyurethane prepolymers using diethylene glycol (DEG) as a chain-extender. Then the prepolymer was used to fabricate the HMDI/PCL-PEG/DEG polyurethane hydrogels by free radical polymerization using benzoyl peroxide (BPO) as a cross-linking agent. The influences of the ratio of polyol on the contact angle, swelling ratio, morphology and cytotoxicity in-vitro of the HMDI/PCL-PEG/DEG polyurethane hydrogel were investigated. The biological behavior of the polyurethane hydrogels was analyzed by studying the cell behavior using the standard biological MTT (3–4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) test. The Fourier transform infrared (FTIR) spectra results showed that the polyurethane hydrogels were successfully synthesized. The change of the molar the ratio of the polyhydric alcohols (PEG and PCL) played important roles in the swelling degree, the contact angle and the pore size. The HMDI/PCL-PEG/DEG polyurethane hydrogel (PCL/PEG = 1:3) was hydrophilic with many more large pores while the polyurethane hydrogel with PCL/PEG = 3:1 had a dense structure. The fibroblastic cell proliferation improved with decreasing relative PEG content; however, there were insignificant differences (P > 0.05) on all days of observation of the samples with various PEG contents compared with the negative control group. The MTT assays revealed that the cells were able to grow and proliferate quite quickly in the extracts of the HMDI/PCL-PEG/DEG polyurethane hydrogels as well as the extract of the negative control.     

Sustained Release of Protein Particle Encapsulated in Bead-on-String Electrospun Nanofibers

The feasibility of alleviating burst release of electrospun bead-on-string nanofiber scaffolds loaded with protein particles was evaluated, including an investigation of the influence of the beads number on the release profile. Bovine serum albumin–loaded dextran particles were used as the model drug and poly(lactic-co-glycolic acid) as the polymer to fabricate the bead-on-string nanofiber scaffolds by electrospinning. Both the bead structure and the distribution of the particles in the beads were examined by scanning electron, transmission electron, and fluorescence microscopy. The results of fluorescence microscopy suggested that the particles were well encapsulated by the beads of the fibers. In vitro release tests showed that a more sustainable release profile with less initial burst release could be obtained from the bead-on-string fibers than from smooth fibers with uniform diameter. In addition, when the number of the forming beads was not numerous enough to encapsulate all the particles in the suspensions, the release performance worsened because the surplus particles were not properly encapsulated.     

Optimization of Release Conditions of Alzheimer's Drug Donepezil Hydrochloride from Sodium Alginate/Sodium Carboxymethyl Cellulose Blend Microspheres

Microspheres of blends of sodium alginate (NaAlg) and sodium carboxymethyl cellulose (NaCMC) were prepared by a water-in-oil (w/o) emulsion crosslinking method and used for the release of donepezil hydrochloride (DP), which is an Alzheimer's drug. The microspheres were characterized with Fourier transform infrared spectroscopy (FTIR), differantial scanning calorimetry (DSC), and scanning electron microscopy (SEM). The microsphere characteristics, including DP entrapment efficiency, particle size, equilibrium swelling degree (ESD), and DP release kinetics, were determined. The effects of the preparation conditions, including the NaAlg/NaCMC (w/w) ratio, drug/polymer (w/w) ratio, cross-linker concentration and time of exposure to the cross-linker, on the release of DP were investigated for successive gastrointestinal tract pH values of 1.2, 6.8, and 7.4 at 37°C. The release of DP increased with the increase in NaAlg/NaCMC (w/w) ratio and drug/polymer (d/p) ratio, while it decreased with increasing extent of cross-linking. The optimum DP release was obtained as 99.13% for a NaAlg/NaCMC (w/w) ratio of 2/1, d/p ratio of 1/4, CaCl₂ concentration of 5% and crosslinking time of 30 min. It was also observed from release results that DP release from the microspheres through the external medium was higher at low pH (1.2) values than that at high pH (6.8 and 7.4) values. The DP release of the microspheres followed either Fickian transport below a value of n < 0.5 or anomalous transport (n = 0.5–1.0).     

Transport properties of Chitosan-Amikacin films

The transport properties of films based on chitosan and a drug have been studied, and sorption and diffusion characteristics of the films have been examined. The calculated diffusion coefficients and the abnormal kinetic curves of amikacin release have been discussed. An analysis of the obtained data showed that the process of drug transport from chitosan films deviated from the classical Fick’s laws due to structural changes in the polymer matrix induced by its chemical modification because of interaction with the drug.     

Biocompatible polymeric implants for controlled drug delivery produced by MAPLE

Implants consisting of drug cores coated with polymeric films were developed for delivering drugs in a controlled manner. The polymeric films were produced using matrix assisted pulsed laser evaporation (MAPLE) and consist of poly(lactide-co-glycolide) (PLGA), used individually as well as blended with polyethylene glycol (PEG). Indomethacin (INC) was used as model drug. The implants were tested in vitro (i.e. in conditions similar with those encountered inside the body), for predicting their behavior after implantation at the site of action. To this end, they were immersed in physiological media (i.e. phosphate buffered saline PBS pH 7.4 and blood). At various intervals of PBS immersion (and respectively in blood), the polymeric films coating the drug cores were studied in terms of morphology, chemistry, wettability and blood compatibility. PEG:PLGA film exhibited superior properties as compared to PLGA film, the corresponding implant being thus more suitable for internal use in the human body. In addition, the implant containing PEG:PLGA film provided an efficient and sustained release of the drug. The kinetics of the drug release was consistent with a diffusion mediated mechanism (as revealed by fitting the data with Higuchi's model); the drug was gradually released through the pores formed during PBS immersion. In contrast, the implant containing PLGA film showed poor drug delivery rates and mechanical failure. In this case, fitting the data with Hixson-Crowell model indicated a release mechanism dominated by polymer erosion.     

An MRI Analysis of the Dissolution of a Soluble Drug Incorporated within an Insoluble Polymer Tablet

Magnetic resonance imaging is used to map the ingress of water into a nominally nonswelling polymer-matrix slow-release drug delivery device comprising a compact of particulate Eudragit polymer and Diltiazem Hydrochloride drug. It is shown that the water ingresses with the square root of time: that is, it is "Fickian-like"; and that the release depends only weakly on the particulate size. A dissolution–diffusion model specifically incorporating the drug particulate size is developed to describe the release mechanism. The experimental results are in accord with the model. It is further shown theoretically that the release should become "non-Fickian-like" and particle size dependent if the drug dissolution constant were to be reduced substantially, an observation explained using a dimensionless scaling argument that compares the dissolution and diffusion rates. It has, however, not been possible to perform experiments in this different regime with the same materials. Authors' address: Peter J. McDonald, Department of Physics, School of Electronics and Physical Sciences, University of Surrey, Guildford, GU2 7XH, UK     

Efficient Synthesis of Submicrometer-Sized Active Pharmaceuticals by Laser Fragmentation in a Liquid-Jet Passage Reactor with Minimum Degradation

One challenge in the development of new drug formulations is overcoming their low solubility in relevant aqueous media. Reducing the particle size of drug powders to a few hundred nanometers is a well-known method that leads to an increase in solubility due to an elevated total surface area. However, state-of-the-art comminution techniques like cryo-milling suffer from degradation and contamination of the drugs, particularly when sub-micrometer diameters are aspired that require long processing times. In this work, picosecond-pulsed laser fragmentation in liquids (LFL) of dispersed drug particles in a liquid-jet passage reactor is used as a wear-free comminution technique using the hydrophobic oral model drugs naproxen, prednisolone, ketoconazole, and megestrol acetate. Particle size and morphology of the drug particles are characterized using scanning electron microscopy (SEM) and changes in particle size distributions upon irradiation are quantified using an analytical centrifuge. The findings highlight the superior fragmentation efficiency of the liquid-jet passage reactor setup, with a 100 times higher fraction of submicrometer particles (SMP) of the drugs compared to the batch control, which enhances solubility and goes along with minimal chemical degradation (<1%), determined by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), high-performance liquid chromatography (HPLC), and X-ray diffraction (XRD). Moreover, the underlying predominantly photo-mechanically induced laser fragmentation mechanisms of organic microparticles (MP) are discussed.     

A nanocomposite material formed by benzofulvene polymer nanoparticles loaded with a potent 5-HT3 receptor antagonist (CR3124)

Poly-BF3a, a new hydrophobic polymer obtained by spontaneous polymerization of 1-methylene-3-phenyl-1H-indene, was found to give nanoparticles characterized by favorable shape and dimensions. Poly-BF3a nanoparticles were loaded with CR3124, a potent 5HT₃ antagonist, as a drug model by desolvation methods either in the absence or in the presence of polyethylene glycol (PEG1000) as a wetting agent. The SEM studies showed that the introduction of CR3124 into the preparation led to a variable degree of aggregation–cementation, which afforded a sort of nanocomposite material. In the absence of PEG1000, the drug molecule was found to stay in the amorphous state (DSC studies) when its percentage is not higher than 10% by weight. In vitro release experiments showed that the formation and stability of the dispersion as well as the drug release were remarkably affected by the presence of PEG1000, demonstrating its beneficial effect to the nanoparticle morphology and disaggregation.     

Polymer-assisted crystallization of low-dimensional lead sulfide particles

PbS micro- and nanoparticles were synthesized by a simple precipitation reaction of lead nitrate with thioacetamide in hydrosoluble polymer water solutions. The effects of four water soluble polymers: polyacrylamide (PAM), polyvinyl alcohol (PVA), polyethylene glycol (PEG) and poly-N-vinyl pyrrolidone (PVP) on the PbS crystallites morphology and structural properties were investigated by scanning electron microscopy (SEM) and X-ray diffraction (XRD). It was found that for the PbS particles obtained in the PVA, PEG and PVP, the (2 0 0) diffraction peak of the nanocrystals becomes dominant. The highest texture in the [2 0 0] direction was observed for the crystallites obtained in the presence of PVP. Polydisperse PbS particles with cubic morphology and size ranging from 100 nm to several microns are obtained in the case of PAM and PEG. Monodisperse cubic PbS crystallites with an average size of 200 nm are formed in the presence of PVA and PVP.     

Graft Polymerization of Methyl Methacrylate- Acrylonitrile onto Poly(ethene-co-1-butene) and Its Toughening Effect on SAN Resin

Poly(ethene-co-1-butene)-graft-methyl methacrylate-acrylonitrile (PEB-g-MAN) was prepared by suspension grafting copolymerization of methyl methacrylate (MMA) and acrylonitrile(AN) onto PEB. PEB-g-MAN/SAN resin blends (ABMS) were prepared by blending PEB-g-MAN with styrene-acrylonitrile copolymer (SAN resin). The effects of AN/(MMA+AN) feed ratio (f_AN), PEB/(PEB+MMA+AN) feed ratio (f_PEB) and benzoyl peroxide (BPO) dosage on the monomer conversion ratio (CR), rubber's grafting ratio (GR), grafting efficiency (GE) of the copolymerization and the toughening effect of PEB-g-MAN on the SAN resin were investigated. FTIR quantitative analysis showed that when the weight percent of AN unit in the unextracted product was 21.5 wt% with f_AN of 25 wt%, the toughening effect of unextracted PEB-g-MAN on SAN resin was the highest. Gel permeation chromatography (GPC) analysis showed that when f_AN was 25 wt%, the grafted copolymer had the lowest molecular weight and ABMS had highest toughness. Transmission electron microscopy (TEM) analysis showed that the highest toughness occurred when the phase structure of ABMS was cocontinuous with f_AN of 25 wt%. When f_AN was 25 wt% PEB-g-MAN domains have numerous small SAN domains in them, which was occlusion structure. Scanning electron microscopy (SEM) analysis indicated that the ABMS fracture surfaces had plastic flow visible, which looked like a craze fibers morphology, for the sample with highest impact strength (f_AN = 25 wt%). Dynamic mechanical thermal analysis (DMA) showed that the miscibility of the PEB phase and SAN phase improved after graft copolymerization of MMA and AN onto PEB.     

Hybrid nanostructured materials with tunable magnetic characteristics

Novel titanium oxide (TiO₂) nanoparticles were fabricated via a modified propanol drying step. These nanoparticles were loaded with anti-cancer drug paclitaxel (PTX) to yield PTX-TiO₂ nanocomposites. The nanocomposites were characterized for their size and surface morphology employing nanoparticle tracking analysis (NTA) and scanning electron microscopy (SEM). The SEM images showed spherical particles with smooth surface and narrow size distribution of ~30–40 nm, which was also supported by NTA analysis data. The drug loading efficiency of the air-dried nanoparticles was observed to be ~63.61 % while those prepared through propanol-induced drying step showed ~69.70 %, thereby demonstrating higher efficiency of the latter. In vitro pH-dependent release of the loaded PTX was observed with higher release at acidic pH compared with physiological pH. Cell uptake studies suggested of time-dependent internalization of nanocomposites with significant improvement in uptake by increasing incubation time from 2 to 24 h, as evidenced by flow cytometry. Further, the cell viability as a measure of anti-cancer activity revealed that cell viability upon exposure to PTX only was 40.5 % while that of PTX-TiO₂ nanocomposite showed 21.6 % viability after 24 h, suggesting better anti-cancer efficacy of nanocomposites. Apoptosis studies revealed that cells treated with PTX-TiO₂ nanocomposites possessed more amount of apoptotic bodies as compared to those treated with PTX only.     

Relationship between Peroxide Initiators and Properties of Styrene Grafted Polypropylene via Reactive Extrusion

To understand the relationship between the initiators and the properties of grafted polypropylene (PP), and provide guidance for designing polymers with different performance through selecting appropriate initiators, a series of styrene (St) grafted PP was prepared by modifying commercial linear PP via reactive extrusion using two different peroxide initiators, dicumyl peroxide (DCP) and benzoyl peroxide (BPO). Fourier transform infrared spectra indicated that the use of DCP led to a higher St grafting degree compared to the system using BPO. The melt flow index and rheological characteristics suggested the existence of short chain branching (SCB) structures in the St grafted PP using DCP, and long chain branching (LCB) structures in the St grafted PP using BPO. Differential scanning calorimetry and polarized optical microscopy results showed that the degradation of the PP chains and the introduction of SCB structures hindered the crystallization process of the St grafted PP using DCP, and the existence of the LCB structures accelerated the crystallization process of the St grafted PP using BPO. We suggest this research can contribute to the understanding of methods to prepare grafted PP with special properties via reactive extrusion by using proper initiators.     

Solute Permeability of Certain Polymeric Films Applied on Aspirin Crystals to Form Microcapsules

A study was carried out to investigate the solute permeability of various polymer films applied on aspirin crystal to form microcapsules. The coating materials were an acrylate methacrylate (AMA), poly 3‐hydroxybutyrate‐hydroxyvalerate (Biopol^®) and poly (lactic‐glycolic) acid (PLGA). Organic solutions of the polymers were applied on the aspirin crystals (core) by a spray coating technique in a Wurster column. The microcapsule surfaces were investigated using scanning electron microscopy (SEM), while permeability studies were carried out on single microcapsules serving as micro dialysis cells. The amount of drug (m) permeating through the applied films in time (t) was analysed on the basis of Fickian diffusion. The SEM revealed numerous surface pores of size range 2.4 to 24 μm for the AMA films, while the PLGA and Biopol films, on the other hand, exhibited very few surface pores of size range 2.2 to 18 μm. However, the AMA films were more spongy than the PLGA and Biopol. The AMA films displayed a retarded release while the PLGA or Biopol films displayed a burst release, attributable to the differences in the film's porous structure. The Permeability coefficient (P) depended on the core weight of the single microcapsules, decreasing with increase in core weight. Thus, for an ensemble of the microcapsules the permeability coefficients of the films of the component microcapsules will have a distribution of P values even though the coating material is the same. This finding is important in the simulation of drug release from coated multiparticulate systems.