Bioadhesive Controlled Metronidazole Release Matrix Based on Chitosan and Xanthan Gum

Metronidazole, a common antibacterial drug, was incorporated into a hydrophilic polymer matrix composed of chitosan xanthan gum mixture. Hydrogel formation of this binary chitosan-xanthan gum combination was tested for its ability to control the release of metronidazole as a drug model. This preparation (MZ-CR) was characterized by in vitro, ex vivo bioadhesion and in vivo bioavailability study. For comparison purposes a commercial extended release formulation of metronidazole (CMZ) was used as a reference. The in vitro drug-release profiles of metronidazole preparation and CMZ were similar in 0.1 M HCl and phosphate buffer pH 6.8. Moreover, metronidazole preparation and CMZ showed a similar detachment force to sheep stomach mucosa, while the bioadhesion of the metronidazole preparation was higher three times than CMZ to sheep duodenum. The results of in vivo study indicated that the absorption of metronidazole from the preparation was faster than that of CMZ. Also, MZ-CR leads to higher metronidazole Cmax and AUC relative to that of the CMZ. This increase in bioavailability might be explained by the bioadhesion of the preparation at the upper part of the small intestine that could result in an increase in the overall intestinal transit time. As a conclusion, formulating chitosan-xanthan gum mixture as a hydrophilic polymer matrix resulted in a superior pharmacokinetic parameters translated by better rate and extent of absorption of metronidazole

Influence of Film Composition on the Morphology, Mechanical Properties, and Surfactant Recovery of Phase-Separated Phospholipid-Perfluorinated Fatty Acid Mixed Monolayers

Monolayer surfactant films composed of a mixture of phospholipids and perfluorinated (or partially fluorinated) surfactants are of potential utility for applications in pulmonary lung surfactant-based therapies. As a simple, minimal model of such a lung surfactant system, binary mixed monolayer films composed of 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC) and perfluorooctadecanoic acid (C18F) prepared on a simplified lung fluid mimic subphase (pH 7.4, 150 mM NaCl) have been characterized in terms of mixing thermodynamics and compressibility (measured through π–<i>A</i> compression isotherms), film morphology (via atomic force, fluorescence, and Brewster angle microscopy), as well as spreading rate and hysteresis response to repeated expansion–contraction cycles for a variety of compositions of mixed films. Under all mixing conditions, films and their components were found to be completely immiscible and phase-separated, though there were significant changes in the aforementioned film properties as a function of composition. Of particular note was the existence of a maximum in the extent of immiscibility (characterized by Δ<i>G</i>_ex^π values) and enhanced surfactant recovery during hysteresis experiments at χ_C18F ≥ 0.30. The latter was attributed to the relatively rapid respreading rate of the perfluorinated amphiphile in comparison with DPPC alone at the air–water interface, which enhances the performance of this mixture as a potential pulmonary lung surfactant. Further, monolayer film structure could be tracked dynamically as a function of compression at the air–water interface via Brewster angle microscopy, with the C18F component being preferentially squeezed out of the film with compression, but returning rapidly upon re-expansion. In general, addition of C18F to DPPC monolayers resulted in improvements to mechanical, structural, and respreading properties of the film, indicating the potential value of these compounds as additives to pulmonary lung surfactant formulations

Influence of Film Composition on the Morphology, Mechanical Properties, and Surfactant Recovery of Phase-Separated Phospholipid-Perfluorinated Fatty Acid Mixed Monolayers

Monolayer surfactant films composed of a mixture of phospholipids and perfluorinated (or partially fluorinated) surfactants are of potential utility for applications in pulmonary lung surfactant-based therapies. As a simple, minimal model of such a lung surfactant system, binary mixed monolayer films composed of 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC) and perfluorooctadecanoic acid (C18F) prepared on a simplified lung fluid mimic subphase (pH 7.4, 150 mM NaCl) have been characterized in terms of mixing thermodynamics and compressibility (measured through π–<i>A</i> compression isotherms), film morphology (via atomic force, fluorescence, and Brewster angle microscopy), as well as spreading rate and hysteresis response to repeated expansion–contraction cycles for a variety of compositions of mixed films. Under all mixing conditions, films and their components were found to be completely immiscible and phase-separated, though there were significant changes in the aforementioned film properties as a function of composition. Of particular note was the existence of a maximum in the extent of immiscibility (characterized by Δ<i>G</i>_ex^π values) and enhanced surfactant recovery during hysteresis experiments at χ_C18F ≥ 0.30. The latter was attributed to the relatively rapid respreading rate of the perfluorinated amphiphile in comparison with DPPC alone at the air–water interface, which enhances the performance of this mixture as a potential pulmonary lung surfactant. Further, monolayer film structure could be tracked dynamically as a function of compression at the air–water interface via Brewster angle microscopy, with the C18F component being preferentially squeezed out of the film with compression, but returning rapidly upon re-expansion. In general, addition of C18F to DPPC monolayers resulted in improvements to mechanical, structural, and respreading properties of the film, indicating the potential value of these compounds as additives to pulmonary lung surfactant formulations

Pentaerythritol-Based Molecular Sorbent for CO₂ Capturing: A Highly Efficient Wet Scrubbing Agent Showing Proton Shuttling Phenomenon

Pentaerythritol (PE) is considered a biodegradable material that combines the ease of synthesis, nonvolatility, and extra stability under basic conditions (acidic gas sequestration, e.g., CO₂), which makes it a useful candidate for postcombustion capture (PCC) application. To overcome corrosion problems associated with CO₂ binding organic liquids, a binary mixture comprised of PE/1,8-diazabicyclo-[5,4,0]-undec-7-ene (DBU) (1:4 molar ratio) dissolved in dimethyl sulfoxide (DMSO) was exploited for CO₂ capturing. The formation of ionic alkyl organic carbonate (RCO₃^– DBUH⁺) was confirmed using ¹³C NMR (157.4 ppm) and ex situ attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) (two peaks were identified, viz., 1670 and 1630 cm^–1, which were ascribed to the symmetric and asymmetric stretching of both CO and O^{<u>···</u>}C^{<u>···</u>}O⁻ within RCO₃H and RCO₃^–, respectively). The charged adduct was measured using a thermostated beaker coupled with conductivity and pH meter probes. The sorption capacity of a 5.0% PE (w/v) solution was measured volumetrically with high efficiencies as, ca. 16 and 18.5 wt %, for wet and dry conditions, respectively. In addition, density functional theory (DFT) was performed to understand the mechanism of action in the case of H₂O, and simple alcohols, e.g., methanol and ethanol. Moreover, we reported on the newly discovered medium-dependent proton shuttling phenomenon that was verified experimentally and theoretically

Unconventional CO₂‑Binding and Catalytic Activity of Urea-Derived Histidines

The development of an ideal sorbent/catalyst for CO2 capturing and fixation into cyclic carbonates under mild conditions is still ongoing. We report on furnishing l-histidine ester dihydrochloride (His-OMe) into a functionalized urea, 5,6,7,8-tetrahydro-7-(methoxycarbonyl)-5-oxoimidazo­[1,5-c]­pyrimidine (His-Urea, 2). The latter is prepared via a microwave and a modified sonochemical approach using propylene carbonate and N,N′-carbonyldiimidazole, which is further functionalized by different mono- or disubstituted alkyl halides with acceptable yields. Upon activation of 2 or its hydroxylated version 4b with NaH, the CO2 capturing in dimethyl sulfoxide is proven to be a dicarboxylated species (carbamide and alkyl carboxylates, 2·2CO2Na) or alkyl carbonate adduct in the case of 4b, as verified by 1H/13C NMR and ATR-FTIR spectroscopies. A first-time preparation of the dimeric ([DiHis-Urea-Pr]­Br, 6) is reported among the prepared bio-based materials. Density functional theory (DFT) calculations confirm the most active reaction site and verify the CO2-sequestrated adducts. Furthermore, the synthesized substrates (2, 4a–b, and 6) are tested for the cycloaddition reaction of epichlorohydrin with CO2 under mild reaction conditions, with good-to-excellent catalytic activity up to quantitative conversions under arbitrary conditions (3.0 mol% catalyst loading, 90 °C, 8 h, 1 atm CO2). The suggested reaction mechanism is verified via DFT calculations, in which the ring closure is the rate-determining step