Celest Samyn

Second-order non-linear optical polymers

In this article we discuss the state of the art in the field of second-order non-linear optical polymers. More specifically, we highlight those results that we think made an important contribution to the field, combined with some of our own results. We start with a general overview of all the aspects involved in characterizing second-order non-linear optical polymers, from thin film formation and poling to second-harmonic generation and electro-optic measurements on such systems. Next, we review the second-order non-linear optical properties of selected polymer systems such as poly(vinyl ether)s, polystyrenes, polymethacrylates, main-chain polymers and high Tg polymers like polyimides and polymaleimides. Finally, we discuss some new polymer systems that might become important in the field of non-linear optics in the near future.

Azo polymers for colon-specific drug delivery

Abstract In order to develop a colon-specific drug delivery system, copolymers of 2-hydroxyethyl methacrylate and methyl methacrylate were prepared in the presence of bis(methacryloylamino)azobenzene. The conditions of polymerization were optimized to prevent crosslinking. Film coatings were prepared with the azo polymers. The films were insoluble in simulated gastric and intestinal juice. Dependent on the of the hydrophilic groups in the polymers, the films were more or less permeable to water. In vitro and in vivo tests prove that it is possible to use the polymers to deliver drugs to the large intestine. Due to the presence of the azo compound, the azo polymer coatings can be degraded by intestinal bacteria.

The Relation Between Swelling Properties and Enzymatic Degradation of Azo Polymers Designed for Colon-Specific Drug Delivery

Copolymers of 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA), and terpolymers of HEMA, MMA, and methacrylic acid (MA) were synthesized in the presence of N,N′-bis(methacryloyloxyethyloxycarbonylamino)azobenzene (B(MOEOCA)AB) and evaluated as coating materials for colonic targeting. The release of ibuprofen, a model drug, from capsules coated with the azo polymers was investigated in vitro. The release medium was made up of sonicated rat cecal content, benzyl viologen, glucose-6-phosphate, glucose-6-phosphate dehydrogenase, and nicotine amide dinucleotide phosphate (NADP) in phosphate buffer (pH 6.8, 0.05M). The drug-release profiles indicate that the degradation of the azo polymer coatings depends on their degree of swelling, due to a higher accessibility of the azo bonds for the bacterial azo reductase. The best results were obtained with azo polymers containing MA: 98.7 (±1.1) % of ibuprofen was released after 19 hours residence in the release medium, while only 26.2 (± 4.9) % in the control experiment. These findings demonstrate that azo polymers are promising materials for delivering drugs selectivity to the colon.

In vivo evaluation of a colon-specific drug delivery system: an absorption study of theophylline from capsules coated with azo polymers in rats.

Azo polymers based upon 2-hydroxyethyl methacrylate, methyl methacrylate, and methacrylic acid, and containing N,N′-bis [(methacryloyloxyethyl)oxy(carbonylamino)]azobenzene as azo aromatic agent were evaluated in vivo as coatings for colon-specific drug delivery. The gastrointestinal absorption of theophylline from capsules coated with the azo polymers was examined in the proximal part of the small intestine and the cecum of male Wistar rats. The capsules were surgically inserted in the region of interest. The plasma concentration of the drug was higher when the capsules were inserted in the cecum as compared to the small intestine. The appearance of theophylline in the plasma when capsules were administered in the small intestine can be attributed to simple diffusion of the drug through the swollen polymer coating. Release and absorption from the cecum is the combined result of diffusion and degradation of the azo polymer coatings by bacterial azo reductase.

Azo polymers for colon-specific drug delivery. II: Influence of the type of azo polymer on the degradation by intestinal microflora

Abstract Degradation by gastrointestinal microflora of different azo polymers was studied by performing permeability experiments on isolated films and solution viscosity measurements before and after incubation in Schaedler broth, inoculated with human feces. The investigated azo polymers were different in monomer composition (hydroxyethyl methacrylate/methyl methacrylate ratio) and azo aromatic group (divinylazobenzene, N , N ′-bis(methacryloylamino)azobenzene and N , N ′-bis(methacryloyloxyethyloxycarbony-lamino)azobenzene). The degradation of the azo polymers was strongly affected by the hydrophilicity of the polymers. The chain length of the azo aromatic groups, built into the azo polymers, seems to be of little influence on the degradation rate of the polymers.

Cycloaddition reactions of azides with electron-poor olefins : Isomerization and thermolysis of the resulting Δ2-triazolines

The cycloaddition reactions of phenyl azide and butyl azide with monosubstituted electronpoor olefins are highly regioselective (if not regiospecific) and lead to 1,4-disubstituted Δ2-triazolines or products derived therefrom: aziridines, diazocompounds, pyrazolines and 1,4-trisubstituted triazolines. As expected, the latter three products are not formed when a methyl group is introduced in the geminal position of the olefins, but Δ2-triazolines and aziridines are then obtained exclusively. In all cases studied the 1,4-substituted Δ2-triazolines derived from phenyl azide only give aziridines on thermolysis, whereas those derived from alkyl azides are thermally converted into a mixture of aziridine and enamine.

Characterization of colon-specific azo polymers: A study of the swelling propertoes and the permeability of isolated polymer films

Abstract In order to prepare azo polymers for colonic targeting, copolymers of 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA), and terpolymers of HEMA, MMA, and methacrylic acid (MA) were synthesized in the presence of different azo compounds. In the present study, the azo polymers were characterized by swelling and permeability studies, performed on isolated films. It was shown that MMA is the swelling capacity and rate determining compound in the azo polymers investigated. Permeability experiments revealed that the diffusion of caffeine as well as the transmission of water vapour is proportional to the concentration of HEMA in the polymers. Hydrophilic plasticizers increase water vapour transmission and diffusion of caffeine through the films. By incorporation of MA into the azo polymers, pH dependency was introduced. The swelling behaviour and diffusion of caffeine are nearly constant over the pH range from 1 to 6. A sharp increase above pH 6, corresponding with the ionization of the carboxylic acid groups appears, with a maximum around pH 8.

Synthesis and characterisation of inulin-azo hydrogels designed for colon targeting

The present paper describes the synthesis and characterisation of new hydrogel systems designed for colon targeting. The gels were composed of methacrylated inulin (MA-IN), copolymerized with the aromatic azo agent bis(methacryloylamino)azobenzene (BMAAB) and 2-hydroxyethyl methacrylate (HEMA) or methacrylic acid (MA). The gels were assessed by studying the influence of various parameters on the dynamic and equilibrium degree of swelling. It was shown that the uptake of water in the gels was inversely proportional to the MA-IN feed concentration, the degree of substitution of the inulin backbone, and the concentration of BMAAB. The latter can probably be explained by the hydrophobic nature and rigidity of the aromatic azo agent. Incorporation of the hydrophilic monomers HEMA or MA also reduced the equilibrium degree of swelling. An increasing network density and hydrogen bonding propensity, can suggested to be responsible for this observation. It was shown that water uptake in the hydrogels was controlled by both relaxation and diffusion mechanisms (anomalous behaviour). When the release of the model drug prednisolone was studied in phosphate buffer, it was shown that >80% of the drug was released during the first 3 h from hydrogels of MA-IN:HEMA. Although drug release decreased significantly from MA-IN:HEMA:BMAAB hydrogels, it remained too high: approximately 50% of the drug was released after 5 h. The same observation was made for hydrogels containing MA instead of HEMA. These results clearly point out the difficulty in finding the optimal balance between swelling to allow degradation in the colon (high swelling of the gels) and low premature drug release before the colonic environment is reached (low swelling properties).

Colonic drug-targeting: In vitro release of ibuprofen from capsules coated with poly(ether-ester) azopolymers

For the purpose of colonic drug-targeting, poly(ether-ester) azopolymers were synthesized and used to coat capsules containing ibuprofen. The release of ibuprofen was studied from coated capsules incubated in the medium prepared by suspending rat caecal contents in phosphate buffer pH 6.8 (RCCRM) and in capsules incubated in plain phosphate buffer (PB). The release of ibuprofen was higher in RCCRM than in PB. This was due to the presence of azoreductase in RCCRM, an enzyme which breaks down azopolymers by reducing azo bonds. Furthermore, the release of ibuprofen was a function of the thickness of the coating, the release being higher the thinner the coating. Addition of polyethylene glycol in the coating solution resulted in capsules with a higher drug release due to enhanced hydrophilicity of the coating. A two-layer coating gave a too early release, while a thick four-layer coating impeded drug release for 24 h. Medium thickness poly(ether-ester) coating containing 15% polyethylene glycol exhibited potential usefulness in colon-targeting of drugs.

Influence of the chromophore ionization potential on speed and magnitude of photorefractive effects in poly(N-vinylcarbazole) based polymer composites

We report on the synthesis of three highly polar chromophores and their use as dopants in poly(N-vinylcarbazole) based photorefractive polymer composites sensitized with (2,4,7-trinitro-9-fluorenylidene)malononitrile. Small alterations in the amino donor group substituents were used to tune the dye’s ionization potential (IP) by 0.2 eV. At 780 nm, 5 °C above the glass transition temperature (Tg), and with an applied field of 59 V/μm, we observed complete internal diffraction and a gain coefficient of 167 cm−1. In this temperature range, diffraction efficiency, gain coefficient, and photorefractive phase shift were found to correlate with the chromophore IP. At 20 °C below Tg, the contribution from birefringence to the index modulation is insignificant, and the speed of the photorefractive effect correlates well with the chromophore IP. Analysis of the results suggests that the space–charge field is influenced by the chromophore IP.