Influence of process parameters on the size distribution of PLA microcapsules prepared by combining membrane emulsification technique and double emulsion-solvent evaporation method

Relatively uniform-sized biodegradable poly(lactide) (PLA) microcapsules with various sizes were successfully prepared by combining a glass membrane emulsification technique and water-in-oil-in-water (w₁/o/w₂) double emulsion-solvent evaporation method. A water phase was used as the internal water phase, a mixture solvent of dichloromethane (DCM) and toluene dissolving PLA and Arlacel 83 was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w₁/o primary emulsion. The primary emulsion was permeated through the uniform pores of a glass membrane into the external water phase by the pressure of nitrogen gas to form the uniform w₁/o/w₂ double emulsion droplets. Then, the solid polymer microcapsules were obtained by simply evaporating solvent. The influence of process parameters on the size distribution of PLA microcapsules was investigated, with an emphasis on the effect of oil-soluble emulsifier. A unique phenomenon was found that a large part of emulsifier could adsorb on the interface of internal water phase and oil phase, which suppressed its adsorption on the surface of glass membrane, and led to the successful preparation of uniform-sized double emulsion. Finally, by optimizing the process parameters, PLA microcapsules with various sizes having coefficient of variation (CV) value under 14.0% were obtained. Recombinant human insulin (rhI), as a model protein, was encapsulated into the microcapsules with difference sizes, and its encapsulation efficiency and cumulative release were investigated. The result suggested that the release behavior could be simply adjusted just by changing precisely the diameters of microcapsule, benefited from the membrane emulsification technique.     

Preparation and characterization of PLGA particles for subcutaneous controlled drug release by membrane emulsification

Uniformly sized microparticles of poly(d,l-lactic-co-glycolic) (PLGA) acid, with controllable median diameters within the size range 40–140 μm, were successfully prepared by membrane emulsification of an oil phase injected into an aqueous phase, followed by solvent removal. Initially, simple particles were produced as an oil in water emulsion, where dichloromethane (DCM) and PLGA were the oil phase and water with stabiliser was the continuous phase. The oil was injected into the aqueous phase through an array type microporous membrane, which has very regular pores equally spaced apart, and two different pore sizes were used: 20 and 40 μm in diameter. Shear was provided at the membrane surface, causing the drops to detach, by a simple paddle stirrer rotating above the membrane. Further tests involved the production of a primary water in oil emulsion, using a mechanical homogeniser, which was then subsequently injected into a water phase through the microporous membrane to form a water in oil in water emulsion. These tests used a water-soluble model drug (blue dextran) and encapsulation efficiencies of up to 100% were obtained for concentrations of 15% PLGA dissolved in the DCM and injected through a 40 μm membrane.

Solidification of the PLGA particles was followed by removal of the DCM through the surrounding aqueous continuous phase. Different PLGA concentrations, particle size and osmotic pressures were considered in order to find their effect on encapsulation efficiency. Osmotic pressure was varied by changing the salt concentration in the external aqueous phase whilst maintaining a constant internal aqueous phase salt concentration. Osmotic pressure was found to be a significant factor on the resulting particle structure, for the tests conducted at lower PLGA concentrations (10% and 5% PLGA). The PLGA concentration and particle size distribution influence the time to complete the solidification stage and a slow solidification, formed by stirring gently overnight, provided the most monosized particles and highest encapsulation efficiency.     

An Efficient Synthesis of (±)-α-Spirovetivene and Related Compounds

A process for the synthesis of (±)-α-spirovetivene starting from I-oxo–2-carbethoxy-6, 10-dimethyl spiro[4.5]dec-6-ene(I)¹ is described. The oxo group of I was reduced by the process of Coates², and the resulting spiro ester (III) and spiro alcohol (IV) were transformed to (±)-α-spirovetivene by the process of Uijttewaal³ and by conventional methods.     

Metal adsorption of carboxymethyl cellulose/carboxymethyl chitosan blend hydrogels prepared by Gamma irradiation

Blend hydrogels based on the carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCts) were prepared by γ-irradiation of a high concentrated CMC/CMCts aqueous solution. Properties of the hydrogels, such as gel fraction, swelling ratio, gel strength, and metal adsorption for Pb and Au were investigated. The gel fraction increased with increasing dose, while the swelling ratio decreased with increasing it. The obtained blend hydrogels had high adsorption performance which was controlled by adjusting the composition of CMC/CMCts.     

A novel method for the synthesis of (Z)-α-selenyl-α,β-unsaturated ketones via acylation of (E)-α-selanylvinylstannanes

The (E)-α-selenylvinylstannanes react with acyl halides in presence of a catalytic amount of Pd(PPh₃)₄ to give the corresponding (Z)-α-selenyl-α,β-unsaturated ketones in good yield.     

Production of α-Tocopherol–Chitosan Nanoparticles by Membrane Emulsification

α-tocopherol (α-T) has the highest biological activity with respect to the other components of vitamin E; however, conventional formulations of tocopherol often fail to provide satisfactory bioavailability due to its hydrophobic characteristics. In this work, α-tocopherol-loaded nanoparticles based on chitosan were produced by membrane emulsification (ME). A new derivative was obtained by the cross-linking reaction between α-T and chitosan (CH) to preserve its biological activity. ME was selected as a method for nanoparticle production because it is recognized as an innovative and sustainable technology for its uniform-particle production with tuned sizes and high encapsulation efficiency (EE%), and its ability to preserve the functional properties of bioactive ingredients operating in mild conditions. The reaction intermediates and the final product were characterized by ¹HNMR, Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), while the morphological and dimensional properties of the nanoparticles were analyzed using electronic scanning microscopy (SEM) and dynamic light scattering (DLS). The results demonstrated that ME has high potential for the development of α-tocopherol-loaded nanoparticles with a high degree of uniformity (PDI lower than 0.2), an EE of almost 100% and good mechanical strength, resulting in good candidates for the production of functional nanostructured materials for drug delivery. In addition, the chemical bonding between chitosan and α-tocopherol allowed the preservation of the antioxidant properties of the bioactive molecule, as demonstrated by an enhanced antioxidant property and evaluated through in vitro tests, with respect to the starting materials.     

Preparation of PTFE-based fuel cell membranes by combining latent track formation technology with graft polymerization

Swift heavy 56 MeV ¹⁵N³⁺ ions were generated with particle fluences of 0, 3×10⁶, 3×10⁷, 3×10⁸, 3×10⁹ ions/cm² to form a latent track zone in a 25-μm-thick film of polytetrafluoroethylene (iPTFE). Styrene (St) was then grafted onto the iPTFE films by UV-irradiation or pre-γ-irradiation, and after sulfonation iPTFE-based proton-conducting membranes were obtained, here called, iPTFE-g(UV)-PStSA and iPTFE-g(γ)-PStSA membranes, respectively, which had a straight cylindrical damage zone around the ion path. The degree of grafting was found to be about 7.5% with a particle fluence of 3×10⁷ ions/cm² and with either the UV-method or the γ-method. The ion-exchange capacity, proton conductivity in the thickness direction, MeOH permeability, tensile strength and elongation at break of the obtained iPTFE-g(UV)-PStSA membrane were 0.50 mmol/g, 0.06 S/cm, 0.15×10⁻⁶ cm²/s, 50 MPa and 600%, in contrast to 0.06 mmol/g, 0.06 S/cm, 0.35×10⁻⁶ cm²/s, 19 MPa and 210% for the iPTFE-g(γ)-PStSA membrane, respectively. In comparison, the Nafion 112 measured in our laboratory exhibited an ion-exchange capacity of 0.91 mmol/g, a proton conductivity of 0.06 S/cm, a MeOH permeability of 1.02×10⁻⁶ cm²/s, a tensile strength of 35 MPa and an elongation at break of 295%. It can be concluded from these data that the lower crossover of MeOH, the same proton conductibility, the lower ion-exchange capacity, and the superior mechanical properties of the UV-grafted proton-conducting membranes compared to the Nafion make them promising materials for widespread application in direct methanol fuel cells. On the other hand, the tests of mechanical strength showed that the PTFE base film is subject to degradation by the ion-beam irradiation as well as the γ-irradiation.     

Shock membrane electropotential drops and limited diffusive distance of β-amyloids in cerebral neurons are detrimental enhancement to Alzheimer's diseases

Molecular physicobiochemical calculations indicated that the metallic ion binding to beta-amyloids (Aβ) may induce production of hydrogen peroxide, which triggers the Ca ion redistribution from the extracellular to the intracellular compartmentation, resulting in a transient membrane electropotential drop by at least 208.06 mV. Moreover, using the Mark and Houwink empirical equation, we predicted that the diffusible distances of all Aβ identities would be confined in a very tiny region within a radius less than 3.96 × 10⁻⁴ cm in brain at 192 h after produced. Because of the inherent tendency of aggregation behaved by the Aβs, the maximum diffusion coefficient and inherent viscosity were 8.24 × 10⁻¹⁵ cm² s⁻¹ and 72.15 cps for the 12 mers (40.8 kDa), the largest soluble form of ABs.Conclusively, we have quantitatively predicted that the shock membrane potential drop (Δφ > 208.06 mV) and limited diffusible distance (<3.96 × 10⁻⁴ cm) in the brain would contribute the major detrimental effects to the neurons in the Alzheimer's diseases.     

The Preparation of β-Cycloalkyl-L-Aspartate and γ-Cycloalkyl-L-Glutamate by Enzymatic Hydrolyses

The simple method to prepare the β-cycloalkyl aspartate and γ-cycloalkyl glutamate by enzymatic reactions has been developed. Compared with conventional chemical methods, the enzymatic method is more facile.     

Preparation,characterization and properties of β-chitin and N-acetylated β-chitin

Free amino groups in β-chitin from squid pen were acetylated to obtain N-acetylated β-chitin. After careful control of degree of acetylation, thermal and mechanical properties of β-chitin and N-acetylated β-chitin were compared. The structural differences of β-chitin and N-acetylated β-chitin were characterized by Fourier transform infrared (FTIR) and wide-angle x-ray diffraction (WAXD) analysis. The results indicated that the crystallinity of N-acetylated β-chitin was higher than that of β-chitin and N-acetylated β-chitin exhibited characteristics similar to α-chitin. Equilibrium water content (EWC) of β-chitin reached to about 50% and this hydrophilic nature was assumed to be caused by a relatively weak hydrogen bonding force of β-chitin with parallel main chains. On the other hand, EWC of N-acetylated β-chitin was 40% due to the introduction of ordered structure. β-chitin and N-acetylated β-chitin have the tensile strength of 0.4 and 0.7 Mpa in the swollen state, respectively. Viscoelastic properties and thermal relaxation behaviors were investigated by dynamic mechanical thermal analysis (DMTA). DMTA spectra of these samples showed that α-transition peaks of β-chitin and N-acetylated β-chitin were observed at 170 and 190°C, respectively. These relaxation peak maxima were assigned to be their glass transition temperature. In addition, a second relaxation peak of β-chitin resulting from acetamide groups was found at 112°C and a broad relaxation peak of N-acetylated β-chitin at around 81–100°C. As a result of thermogravimetric analysis, 10% weight loss temperatures of β-chitin and N-acetylated β-chitin were 270 and 285°C, respectively. © 1996 John Wiley & Sons, Inc.     

A Novel Method for the Synthesis of α,β‐Unsaturated Amides Mediated by Samarium Diiodide

Promoted by Samarium diiodide (SmI₂), α,β‐unsaturated amides were formed from nitrogen anions (formed in situ by the reduction of nitro compounds) and α,β‐unsaturated esters. This reaction contrasts with the conjugate addition between amines and α,β‐unsaturated esters promoted by samarium triiodide (SmI₃) and provides an alternative attractive way to obtain α,β‐unsaturated amides using SmI₂.     

γ(δ)-Thionolactones – Enantioselective Capillary GC and Sensory Characteristics of Enantiomers

The even numbered γ(δ)-thionolactones (C₆–C₁₂) were investigated, using heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl)- and heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin as chiral stationary phases in capillary gas chromatography. The odor characteristics of γ(δ)-thionolactone enantiomers were investigated by enantioselective gas chromatography/olfactometry.     

Photoinduced transformation of α,β-epoxyketones to β-hydroxyketones by Hantzsch 1,4-dihydropyridine

Irradiation (λ >300 nm) of Hantzsch 1,4-dihydropyridine with aromatic α,β-epoxyketones in acetonitrile selectively breaks the Cα---O bond of the epoxides giving the corresponding β-hydroxyketones in excellent yields.     

Examining the levels of ganglioside and cholesterol in cell membrane on attenuation the cytotoxicity of beta-amyloid peptide

The deposition of beta-amyloid (Abeta) on cell membranes is considered as one of the primary factors in having Alzheimer's disease (AD). Recent studies have suggested that certain components of plasma membrane, ganglioside and cholesterol could accelerate the accumulation of Abeta on the plasma membranes. However, the effect of cholesterol and ganglioside (GM1) on Abeta cytotoxicity is still a controversial issue. The aim of this study is to understand the roles of GM1 and cholesterol in AD by using PC12, a neuron-like cell. The effects of the sequence, conformation, and concentration of Abeta on cytotoxicity were also investigated. Monomeric Abeta could attack the plasma membrane resulting in cytotoxicity, however, fibrillar Abeta was found to be less toxic. Our results showed that Abeta (1-40) was more toxic than Abeta (25-35) and the cytotoxicity of Abeta was proportional to its concentration. Besides, the depletion of GM1 from plasma membrane, it would block the Abeta-induced cytotoxicity. Decreasing the cholesterol level by around 30% could attenuate the cytotoxicity of Abeta. These findings validate our idea that the cholesterol could stabilize the lateral pressure derived from the formation of GM1-Abeta complex on the membrane surface. Furthermore, both GM1 and cholesterol are essential in mechanism of Abeta accumulation and could modulate the cytotoxicity of monomeric Abeta.     

Synthesis of β‐Haloketones by β‐Addition Reactions of α,β‐Unsaturated Ketones with BX3 (X = Br,Cl) as Halide Source

A series of β‐bromoketones and β‐chloroketones were synthesized by the addition reactions of α,β‐unsaturated ketones under BX₃ (X = Br, Cl) and ethylene glycol reaction system. The α,β‐unsaturated ester also was successfully converted to its corresponding β‐bromoester under the reaction condition.     

Structural determination and complete NMR spectral assignments of a new diterpenoid obtained from triptonide by biotransformation

A new diterpenoid, 12β,13α‐dihydroxytriptonide, was obtained from the transformed culture of triptonide by Catharanthus roseus cell suspension cultures. The complete ¹H and ¹³C NMR assignments of the compound were carried out by using DEPT, COSY, HSQC, g‐HMBC and NOESY techniques. Copyright © 2003 John Wiley & Sons, Ltd.     

Gas chromatographic separation of the enantiomers of flumecinol and some related compounds

Flumecinol and related compounds can, without derivatization, be separated into their enantiomers by gas chromatography on cyclodextrin phases; permethylated β-cyclodextrin dissolved in OV-1701 can be particularly recommended. Thermodynamic data describing the different intensities of interaction of the individual enantiomers with the stationary phases were determined. The values measured imply different separation mechanisms for the compounds investigated.     

Preparation of high-permeance MFI membrane with the modified secondary growth method on the macroporous α-alumina tubular support

MFI membrane with high permeance was successfully synthesized on the macroporous (pore size of 3–4 μm) α-Al₂O₃ tubular support with a novel modified secondary growth method. Before the crystallization, the seeded support was wrapped with Teflon tape in order to focalize the growth of crystals in the region of seed layer. The as-synthesized membrane was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and single-gas permeation testing. The results indicated that the as-synthesized membrane had a thickness of 6–8 μm similar to the thickness of the seed layer and exhibited high gas permeance. At room temperature, the permeance of H₂ and the ideal separation factor of H₂/SF₆ reached 1.64 × 10⁻⁶ mol m⁻² s⁻¹ Pa⁻¹ and 71, respectively. The permeance of single-gas increased with the increasing of temperature. The ideal separation factors of H₂/i-C₄H₁₀ and H₂/SF₆ decreased with the increasing of temperature from 298 to 473 K. At 473 K, the ideal separation factors of H₂/i-C₄H₁₀ and H₂/SF₆ were 12.16 and 11.08, which were still higher than their Knudsen ratios of 5.39 and 8.54, respectively.     

A Convenient and Versatile Method for the Preparation of α‐Hydroxymethyl Ketone Derivatives from the Corresponding Allyl Silyl Ethers or Allyl Carboxylates

The ozonolysis of 1‐substituted allyl silyl ethers or 1‐substituted allyl carboxylates followed by treatment with bases gave the corresponding α‐silyloxymethyl‐ or α‐acyloxymethyl‐ketones in good yields. It is proposed to proceed via the corresponding α‐silyloxy‐ or α‐acyloxyaldehydes intermediates followed by 1,4‐group migration. The results of theoretical calculations are applicable to explain the experimental results.