Chitosan/TPP microparticles obtained by microemulsion method applied in controlled release of heparin.

This work deals with the preparation of chitosan/tripolyphosphate microparticles (CHT/TPP) using microemulsion system based on water/benzyl alcohol. The morphology of the microparticles was evaluated by scanning electron microscopy (SEM). The microparticles were also characterized through infrared spectroscopy (FTIR) and wide-angle X-ray scattering (WAXS). The morphology and crystallinity of microparticles depended mainly on CHT/TPP ratio. Studies of controlled release of HP were evaluated in distilled water and in simulated gastric fluid. Besides, the profile of HP releasing could be tailored by tuning the CHT/TPP molar ratio. Finally, these prospective results allow the particles to be employed as site-specific HP controlled release system.

Tuning the viscoelastic properties of bis(urea)-based supramolecular polymer solutions by adding cosolutes.

Polymers formed by the self-assembly of a bis(urea)-based polymer, 2,4-bis(2-ethylhexylureido)toluene (EHUT), in organic solvents such as octane are promising systems with remarkable rheological properties. This is the first self-assembled polymer recently reported as a hydrodynamic drag reducer for hydrocarbons. The rheology of diluted and semidiluted EHUT solutions can be tuned by specific interactions between the chains, modulated by the nature of the solvent and the presence of additives. In this article, rheological, thermal and SANS measurements were performed in order to investigate the competition between EHUT self-assembly and its interaction with specific molecules (benzene, benzyl alcohol, and ethanol) that can interact with EHUT unimers via hydrogen bonds and π-π interactions. No substantial rheological, thermal, or structural effect is observed when benzene is added to the systems. However, ethanol and benzyl alcohol interact with EHUT unimers through hydrogen bonds, drastically decreasing the viscoelasticity of the solutions. In addition, benzyl alcohol can interact with EHUT polymers by π-stacking interactions, playing an important role in tuning the rheological properties of the systems.

Prevention of benzyl alcohol-induced aggregation of chymotrypsinogen by PEGylation.

OBJECTIVES: Addition of the antimicrobial preservative benzyl alcohol to reconstitution buffer promotes the formation of undesirable aggregates in multidose protein formulations. Herein we investigated the efficiency of PEGylation (attachment of poly(ethylene glycol)) to prevent benzyl alcohol-induced aggregation of the model protein α-chymotrypsinogen A (aCTgn). METHODS: Various PEG-aCTgn conjugates were prepared using PEG with a molecular weight of either 700 or 5000 Da by varying the PEG-to-protein ratio during synthesis and the formation of insoluble aggregates was studied. The effect of benzyl alcohol on the thermodynamic stability and tertiary structure of aCTgn was also examined. KEY FINDINGS: When the model protein was reconstituted in buffer containing 0.9% benzyl alcohol, copious amounts of buffer-insoluble aggregates formed within 24 h (>10%). Benzyl alcohol-induced aggregation was completely prevented when two or five molecules of PEG with a molecular weight of 5000 Da were attached to the protein, whereas two or four molecules of bound 700 Da PEG were completely inefficient in preventing aggregation. Mechanistic investigations excluded prevention of structural perturbations or increased thermodynamic stability by PEGylation from being responsible for the prevention of aggregation. Simple addition of PEG to the buffer was also inefficient and PEG had to be covalently linked to the protein to be efficient. CONCLUSIONS: The most likely explanation for the protective effect of the 5000 Da PEG is shielding of exposed hydrophobic protein surface area and prevention of protein-protein contacts (molecular spacer effect).

Oligomerization of 3,5-dimethyl benzyl alcohol promoted by clay: experimental and theoretical study.

Linear oligomerization of 3,5-dimethyl benzyl alcohol is induced by a montmorillonite clay (Tonsil Optimum Extra), producing 1,3,5,7-tetramethyl-9,10-dihydro-anthracene, which, by loss of protons results in the product 1,3,5,7-tetramethylanthracene. It was also found that the compounds 4-(3´,5´-dimethylbenzyl)-1,3,5,7-tetramethyl-9,10-dihydroanthracece and 4-(3´,5´-dimethylbenzyl)-1,3,5,7-tetra-methylanthracene were formed from 1,3,5,7-tetramethyl-9,10-dihydroanthracene. 1,3,5,7-Tetramethylanthryl radical cation was formed from 1,3,5,7-tetramethyl-9,10-dihydroanthracene; it was characterized by Electronic Paramagnetic Resonance (EPR). On the other hand, a theoretical analysis was performed, allowing the rationalization of the observed products and some of the key reaction steps.

Nanometer- and submicrometer-sized hollow spheres of chondroitin sulfate as a potential formulation strategy for anti-inflammatory encapsulation.

PURPOSE: The synthesis of nanometer and submicrometer hollow particles could be a motivating way to imprint new therapeutic properties into a chondroitin sulfate-based hydrogel formulation. The use of hollowed polymer structures as a formulation strategy is expected to have an impact in the effective therapy in the treatment of rheumatoid arthritis. METHODS: Chemical modification of the chondroitin sulfate with glycidyl methacrylate (GMA) was performed in water under thermal and acid stimuli. The hydrogel spheres were formed upon cross-linking reaction of modified chondroitin sulfate (CSM) in a water-in-benzyl alcohol nano-droplet emulsion. RESULTS: 1H NMR and 13C NMR spectra showed that the carbon-carbon pi-bonds coming from the GMA were incorporated onto backbones of CS. 13C-CP/MAS NMR spectra revealed that the formation of the CSM hydrogel spheres during the dispersion stage occurred by way of carbon-carbon pi-bonds on the CSM structure. The spherical shapes of the particles with diameters in the range of 20 microm to 500 nm were very clearly verified by SEM images where the dark center and edge of the hollow spheres could be identified easily. CONCLUSIONS: Nanometer- and submicrometer-sized hydrogel spheres with hollow interior were produced from chondroitin sulfate by using a new strategy of hydrogel synthesis.

Photopolymerization of N,N-dimethylaminobenzyl alcohol as amine co-initiator for light-cured dental resins.

OBJECTIVE: The present study was carried out in order to assess the suitability of N,N-dimethylaminobenzyl alcohol (DMOH) as co-initiator of camphorquinone (CQ) and 1-phenyl-1,2-propanedione (PPD) in light-cured dental resins. METHODS: DMOH was synthesized and used as co-initiator for the photopolymerization of a model resin based on {2,2-bis[4-(2-hydroxy-3-methacryloxyprop-1-oxy)phenyl]propane} (Bis-GMA)/triethylene glycol dimethacrylate (TEGDMA). Experimental formulations containing CQ or PPD in combination with DMOH at different concentrations were studied. The photopolymerization was carried out by means of a commercial light-emitting diode (LED) curing unit. The evolution of double bonds consumption versus irradiation time was followed by near-infrared spectroscopy (NIR). The photon absorption efficiency (PAE) of the photopolymerization process was calculated from the spectral distribution of the LED unit and the molar absorption coefficient distributions of PPD and CQ. RESULTS: DMOH is an efficient photoreducer of CQ and PPD resulting in higher polymerization rate and higher double bond conversion compared with dimethylaminoethylmethacrylate. The PAE for PPD was higher than that for CQ. However, the polymerization initiated by PPD progressed at a lower rate and exhibited lower values of final conversion compared with the resins containing CQ. This observation indicates that the lower polymerization rate of the PPD/amine system should be explained in terms of the mechanism of generating primary radicals by PPD, which is less efficient compared with CQ. SIGNIFICANCE: The DMOH/benzoyl peroxide redox system, has recently been proposed as a more biocompatible accelerator for the polymerization of bone cements based on poly(methyl methacrylate), because cytotoxity tests have demonstrated that DMOH possesses better biocompatibility properties compared with traditional tertiary amines. The results obtained in the present study reveal the suitability of the CQ/DMOH initiator system for the polymerization of light-cured dental composites.

Orientation and dynamics of benzyl alcohol and benzyl alkyl ethers dissolved in nematic lyotropic liquid crystals. 2H NMR and molecular dynamics simulations.

Most drugs have to cross cell membranes to reach their final target. A better understanding of the distribution, interactions, and dynamics of biologically active molecules in model bilayers is of fundamental importance in understanding drug functioning and design. 2H NMR quadrupole splittings (delta nu(Q)) and longitudinal relaxation times (T1) from the aromatic ring of benzyl alcohol-d5 (C0), a commonly used anesthetic, and a series of linear alkyl benzyl-d5 ethers with chain lengths from 1 to 12 carbon atoms (C1-C12), were measured. The molecules were dissolved in a nematic discotic lyotropic liquid crystal solution made of tetradecyltrimethylammonium chloride (TTAC)/decanol (DeOH)/NaCl/H2O. Values of delta nu(Q) and T1 from 1,1-dideuteriodecanol (15% enriched) and DHO (H2O with 0.2% D2O) were also measured. Delta nu(Q) of DeOH and DHO remained constant throughout the series. The value of delta nu(Q) of the para position of the ring (delta nu(p)) in C1 is 30% smaller than the delta nu(p) of C0. This is attributed to the existence of an H-bond between the alcohol hydroxyl proton and the solvent, which influences the average orientation of the ring. The relaxation data show that T1o,m is always longer than T1p and both decrease with the increase in alkyl chain length. Molecular dynamics simulations of the experimentally studied systems were performed. The aggregate was represented as a bilayer. The distribution, average orientation, and order parameters of the aromatic ring of the guest molecules in the bilayer were examined. Rotational correlation functions of all the C-D bonds and the OH bond from H2O were evaluated, allowing an estimate of the correlation times and T1. According to these results all spins relax in extreme narrowing conditions, except DeOH. Experimental and calculated T1 values differ at most by a factor of 3. However, the order of magnitude and the observed trends are well reproduced by the calculations. The aromatic ring of C0 possesses a unique average orientation in the bilayer. For the ether series, the orientation is modified and the C2 symmetry axis of the aromatic ring is exchanging between two orientations averaging the quadrupole splittings from the ortho and meta positions. The simulation supports the existence of an H-bond between C0 and the solvent not found in the ethers, which should be responsible for the observed differences.