Controlled Release of Lysozyme Using Polyvinyl Alcohol-Based Polymeric Nanofibers Generated by Electrospinning.

Polymeric nanofibers generated via electrospinning offer a promising platform for drug delivery systems. This study examines the application of electrospun polyvinyl alcohol (PVA) nanofibers for controlled lysozyme (LZM) delivery. By using various PVA grades, such as the degree of polymerization/hydrolysis, this study investigates their influence on nanofiber morphology and drug-release characteristics. LZM-loaded PVA monolithic nanofibers having 50% drug content exhibit efficient entrapment, wherein rapid dissolution is achieved within 30 min. The initial burst of LZM from the nanofiber was reduced as the LZM content was lowered. The initial dissolution is greatly influenced by the choice of PVA grade used; fully hydrolyzed PVA nanofibers demonstrate controlled release due to the reduced water solubility of PVA. Furthermore, coaxial electrospinning, which creates core-shell nanofibers with polycaprolactone as a controlled release layer, enables sustained LZM release over an extended period. This study confirms a correlation between PVA characteristics and controlled drug release and provides valuable insights into tailoring nanofiber properties for pharmaceutical applications.

Formulation Development of Mucoadhesive Microparticle-Laden Gels for Oral Mucositis: An In Vitro and In Vivo Study.

In order to relieve pain due to oral mucositis, we attempted to develop mucoadhesive microparticles containing indomethacin (IM) and gel preparations with IM microparticles that can be applied to the oral cavity. The mucoadhesive microparticles were prepared with a simple composition consisting of IM and polyvinyl alcohol (PVA). Two kinds of PVA with different block properties were used, and microparticles were prepared by heating-filtration and mixing-drying. From the X-ray powder diffraction patterns, differential scanning calorimetry thermograms, and morphological features of the IM microparticles, IM should exist as polymorphic forms in the microparticles. Rapid drug release properties were observed in the IM microparticles. Increased drug retention was observed in IM microparticles containing PVA, and the IM-NK(50) gel, using a common block character PVA and heating-filtration, showed good long-term drug retention properties. In vivo experiments showing significantly higher drug concentrations in the oral mucosa were observed with IM microparticles prepared by heating-filtration, and the IM-NK(50) gel maintained significantly higher drug concentrations in the oral mucosa. From these results, the IM-NK(50) gel may be useful as a preparation for relieving oral mucositis pain.

Computational study on the reaction pathway of α-bromoacetophenones with hydroxide ion: possible path bifurcation in the addition/substitution mechanism.

The reaction of an α-haloketone with a nucleophile has three reaction channels: carbonyl addition, direct substitution, and proton abstraction. DFT calculations for the reaction of PhCOCH(2)Br with OH(-) showed that there exists an addition/substitution TS on the potential energy surface, in which OH(-) interacts with both the α- and carbonyl carbons. The intrinsic reaction coordinate calculations revealed that the TS serves as the TS for direct substitution for XC(6)H(4)COCH(2)Br with an electron-donating X or a X less electron-withdrawing than m-Cl, whereas the TS serves as the TS for carbonyl addition for derivatives with a X more electron-withdrawing than m-CF(3). Trajectory calculations starting at respective TS indicated that the single TS can serve for the two mechanisms, substitution and addition, through path bifurcation after the TS for borderline substrates. The reaction is the first example of dynamic path bifurcation for fundamental reaction types of carbonyl addition and substitution.

Proton-transfer reactions of nitroalkanes: the role of aci-nitro species.

Proton-transfer reactions of two systems, ionization of a series of small carbon acids in water (the Pearson system) and reactions of substituted phenylnitromethanes, were examined in detail computationally. Comparison of experimental reactivity and pK(a) with calculated relative activation barrier and reaction energy for the Pearson system suggested that the origin of the well-know nitroalkane anomaly does not reside in the reactivity but in the equilibrium. For the reactions of substituted phenylnitromethanes, proton transfers among three species, PhCH(2)NO(2), PhCHNO(2)(-), and PhCH=NO(2)H, were examined, and the role of the aci-nitro species (PhCH=NO(2)H) was evaluated on the basis of its stability and reactivity. Protonation of PhCHNO(2)(-) by H(2)O was suggested to occur kinetically on the oxygen site, but due to its instability PhCH=NO(2)H does not contribute to the overall reaction energetics. The protonation of PhCHNO(2)(-) under acidic conditions occurs on the oxygen site to give PhCH=NO(2)H both kinetically and thermodynamically. The aci-nitro species thus formed appears to give PhCH(2)NO(2) via intramolecular H(2)O-mediated proton transfer, but a possibility of the route through PhCHNO(2)(-)-C-protonation would not be fully eliminated.

Deprotonation of 3(2H)-furanone and 3(2H)-thiophenone by carbanions in the gas phase: disproportionately high aromaticity of the transition state: an ab initio study.

The reversible deprotonation of 3(2H)-furanone (3H-O) and 3(2H)-thiophenone (3H-S) by a series of delocalized carbanions and by CN(-), and the identity proton transfer of 3H-O to its conjugate base (3(-)-O) and of 3H-S to 3(-)-S have been studied at the MP2//6-31+G** level. The main objective has been to examine to what extent the aromaticity of 3(-)-O and 3(-)-S is expressed at the transition state of these reactions and how the intrinsic barriers are affected by the transition state aromaticity. Aromaticity parameters such as NICS values, HOMA and Bird Indices indicate a disproportionately high degree of aromatic stabilization of the transition state. This stabilization results in a reduction of the intrinsic barriers which is most clearly manifested in the identity reactions. However, these reductions are relatively modest compared to those reported previously for the identity proton transfers from the benzenium ion to benzene and of cyclopentadiene to its conjugate base, reflecting the smaller aromatic stabilization of 3(-)-O and 3(-)-S compared to those of benzene and cyclopentadienyl anion.