pH-Dependent Release from Monoolein Cubic Phase Containing Hydrophobically Modified Chitosan

Monoolein (MO) cubic phase incorporating hydrophobically modified chosan (Hm chitosan) was prepared to obtain a pH-dependent release. Following calorimetric study, Hm chitosan had little effect on the crystal structure of MO cubic phase under acidic condition where Hm chitosan is readily soluble. At a higher pH (e.g., pH 9.0), however, the crystal structure of MO cubic phase was disturbed, possibly due to the insolubilization of Hm chitosan at the alkali condition. Whether the dye included in the cubic phase is anionic (amaranth) or cationic (methylene blue), the release from the cubic phase was suppressed as the pH of release medium increased. The structural change of cubic phase caused by the insolubilization of Hm chitosan, or the blockage of the water channel of the cubic phase by precipitated Hm chitosan would be responsible for the suppressed released.     

Monoolein cubic phase containing alginate/cystamine gel for controlled release of epidermal growth factor

Monoolein (MO) cubic phase including alginate and cystamine in its water channel controlled the release of epidermal growth factor (EGF) by responding to changes in pH value and the reductive conditions of the release medium. The crosslinking degree of alginate gel with cystamine and the complex coacervation of alginate and EGF were investigated by using light scattering. TEM micrographs of cubic phases revealed MO bilayers along with water channels. Differential scanning calorimetry indicated that the cubic-to-hexagonal phase transition took place at 60.2?°C. Additives such as stearyl trimethyl ammonium chloride and cystamine decreased the transition temperature by a few to more than 10?°C. The release of EGF loaded in cubic phases was completed in 5?h and, thereafter, no significant additional release was observed. The release % of EGF loaded in MO cubic phase containing alginate and cystamine increased not only with the increase of pH but also glutathione concentration. The MO cubic phase containing alginate/cystamine gel can be used as a carrier for the delivery of peptide and protein drugs.     

Monoolein cubic phase including in situ ionically gelled alginate and its salt-responsive release property

Salt-responsive monoolein (MO) cubic phase was prepared by in situ ionically gelling alginate contained in its water channels. On the TEM micrographs, bilayers, and water channels, characteristic of MO cubic phase were observed, and alginate and CaCl₂ had little effect on the structure. According to the differential scanning calorimetric thermogram, the cubic-to-hexagonal phase transition temperature of the cubic phase containing CaCl₂ solution was 46.8°C and it was much lower than that of the cubic phase containing distilled water, 60.5°C. The transition temperature was not significantly affected by alginate. The phase transition temperatures measured by the calorimetric analysis were in accordance with those determined by polarized optical microscopy. An initial burst release of dye (i.e., amaranth) was observed when the gelled alginate was not contained in the water channel of the cubic phase. A sustained release was obtained with the cubic phase containing the gelled alginate. The release of dye loaded in the cubic phase containing the gelled alginate was significantly promoted when the cubic phase came into contact with PBS (10?mM, pH 7.4), possibly because the multivalent cation (Ca²⁺) bound to alginate chains could be replaced by the monovalent cation (Na⁺).     

Monoolein cubic phase containing azobenzene and its UV/visible light irradiation-dependent release property

Monoolein (MO) cubic phase, whose MO/azobenzene mass ratios were 1:0, 1:0.0025, 1:0.005, and 1:0.025, was prepared by a melt-hydration method. According to the polarized optical micrographs and the differential thermograms, the phase transition temperature of the cubic phase was lower as the content of azobenzene was higher, and it decreased upon the subsequent irradiation of UV light for 1 hour and visible light for 1 hour. The photoirradiation significantly promoted the release of methylene blue (a water-soluble dye) loaded in the cubic phase only when the MO/azobenzene mass ratio was 1:0.025. The photoirradiation could promote the release of Nile red (an oil-soluble dye) even when the MO/azobenzene mass ratio was less than 1:0.025. The higher photo-susceptibility of Nile red release was possibly because the dye would be intercalated in the MO lipid matrix and the photoirradiation could affect the lipid matrix property.     

In vitro skin permeation of cubosomes containing water soluble extracts of Korean barberry

The monoolein (MO) cubic phases containing water soluble extract (WSE) from Berberis koreana (Korean barberry) were prepared by hydrating the molten MO with aqueous solutions of WSE (0.5, 1.0, and 1.5%). The phase transition temperature of cubic phase containing WSE (∼70°C) was almost the same as that of WSE-free MO cubic phase that indicates that WSE was immobilized in the water channels of the cubic phase and did not affect its structure. The release of WSE from the cubic phase fits the first order process. The cubosomes were obtained by micronizing the cubic phase in a sonicator using Pluronic F127 as a dispersant. The cubosomes were stable in size at the ethanol concentration ≲16%. When compared with WSE solution in phosphate-buffered saline (10 mM, pH 7.4), in vitro skin permeation of WSE in the cubosomes was enhanced by about two times.     

甘油单油酸脂/水立方液晶体系流变性质的研究

Monoglyceride (MO) can form various liquid crystalline phases spontaneously in the presence of various amount of water at room temperature. The appropriate compositions from binary phase diagram of MO/H2O were selected to form cubic phases. The selected systems were studied at different salt concentrations and pH value using rheological methods. There was a weak effect of salt on viscoelastic properties of cubic phases formed from MO/H2O system. Hexagonal phase was formed when pH value was decreased or increased. The viscoelasticity of cubic phases was different from that of hexagonal liquid crystals. Rheological properties of MO/H2O cubic phases were stable at pH and salt concentration similar to physiological condition.     

Tripolyphosphate-responsive release property of monoolein cubic phase containing sodium dodecyl sulfate and oligo chitosan

Tripolyphosphate (TPP)-responsive MO cubic phase was prepared by immobilizing oligo chitosan in the water channel through its electrostatic attraction with sodium dodecyl sulfate (SDS). The phase transition temperature (PTT) increased with increasing the content of SDS. The PTT of cubic phase whose SDS content was 0%, 0.21%, 0.42%, 0.84%, and 1.68%, determined by polarized microscopy, was about 69.5°C, 72°C, 75°C, 80.5°C, and 95°C, respectively. The PTT did not markedly deviate from that determined by differential scanning calorimetry. The release degree for 72 h of dye (i.e., amaranth and methylene blue) was dependent on the pH value of release medium (pH 3.0 and pH 7.0). Moreover, the release degree significantly increased when the TPP concentration in the release medium increased to 0.4% (w/v). Oligo chitosan was electrostatically complexed with TPP and the complexation took place extensively at the oligo chitosan/TTP mass ratio of 1:0.125 and 1:0.25 and at the oligo chitosan concentration of 1.6% (w/v), evidenced by optical spectroscopy and scanning electron microscopy. It was thought that the complexation was responsible for the TPP concentration-dependent release.     

Monoolein cubic phases containing hydrogen peroxide

Monoolein (MO) cubic phases were prepared by hydrating MO using distilled water or 12 wt.% H₂O₂ solution so that the content of aqueous phase in the cubic phase is 30 wt.%. The thermal transition of the isotropic cubic phase to reversed hexagonal phase was observed on a polarizing photomicroscope and the transition temperature was found to be around 65 °C on a differential scanning calorimeter (DSC). Small-angle X-ray scattering (SAXS) patterns indicated the cubic phases had diamond surfaces. The cubic phase released H₂O₂ into an aqueous phase in a saturation manner so that approx. 50% of total loaded H₂O₂ release in the first 10 h and thereafter relatively slow was observed over 40 h. The cubic phase was stable at 45 °C for 56 days before it broke down into an oily phase and an aqueous phase in 70 days. According to ¹H NMR spectrum, glycerol moiety and ---CH₂=CH₂--- of the oily phase were detected less in number than those of intact MO. Therefore, the hydrolysis and the oxidation of MO would be responsible for the breakdown of the cubic phase. The tensile adhesive forces of the cubic phases were higher than a skin-adhesive patch prepared using polyacrylate. The cubic phase containing H₂O₂ could be used as a topical disinfected gel for a wounded skin.     

Thermo- and UV Photo-Triggerable Monoolein Cubic Phase Bearing Poly(Hydroxyethyl Acrylate-co-Coumaryl Acrylate-co-Octadecyl Acrylate)

Thermo- and UV photo-triggerable monoolein (MO) cubic phases were developed by incorporating poly(hydroxyethyl acrylate-co-coumaryl acrylate-co-octadecyl acrylate) (P(HEA-CA-ODA)) in the cubic phases. P(HEA-CA-ODA)s, for which the HEA/CA/ODA molar ratio was 98.6:0:1.4, 96.7:2.0:1.3, 96.2:2.6:1.2, 95:3.8:1.2, and 92.8:6.1:1.1, calculated on the ¹H NMR spectra, were prepared by a free radical reaction. The air–water interfacial tension was inversely proportional to the CA content of the copolymer. The copolymers for which the CA content was 2.6%, 3.8%, and 6.1% exhibited their phase transition temperature in an aqueous solution in the temperature range from 25°C to 40°C. As the CA content was more, the temperature sensitivity was higher and the phase transition temperature was lower. The UV light (254 nm, 6 W)-induced dimerization degree of CA was proportional to its content in the copolymers. The release of fluorescein isothiocyanate-dextran from cubic phases containing P(HEA/CA/ODA)s was promoted by UV light irradiation, possibly due to the photo-induced collapse of the copolymer chains. The release from cubic phases incorporating copolymers, for which the CA content was 3.8% and 6.1%, was enhanced by increasing the releasing medium temperature from 23°C to 37°C, possibly due to the thermal collapse of the copolymer chains.     

pH and glucose dually responsive injectable hydrogel prepared by in situ crosslinking of phenylboronic modified chitosan and oxidized dextran

Injectable hydrogels with pH and glucose triggered drug release capability were synthesized based on biocompatible phenylboronic modified chitosan and oxidized dextran through the formation of covalent imine bond and phenylboronate ester. Rheological characterization demonstrated that the gelation rate was rapid, and the moduli of the hydrogels were able to be tuned with chemical composition as well as pH and glucose concentration of the polymer solution. Anticancer drugs could be incorporated inside the hydrogel through the in situ gel forming process and undergo a controlled release by altering pH or glucose concentration. The hydrogels had good biocompatibility with viable and proliferated cells cultured in the three dimensional matrix, and the cell proliferation was suppressed when a small amount of DOX was added, which is benefit for the application of the hydrogels as smart anticancer drug delivery system. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1235–1244     

Preparation of microparticles composed of cinnamoyl gelatin and cinnamoyl alginate by spray-drying method and effect of UV irradiation and pH value on their release property

Microparticles composed of cinnamoyl gelatin (CinGel) and cinnamoyl alginate (CinAlg) were prepared as a UV irradiation- and pH-responsive carrier by a spray-drying method. CinGel and CinAlg were prepared by a condensation reaction. Using a colorimetric method, the gelatin to CA mass ratio and the alginate to CA mass ratio were calculated to be 1:0.04 and 1:0.02, respectively. The complexation of CinGel and CinAlg in aqueous solution took place when the medium was acidic (e.g., pH 4.0) and the maximum complexation was obtained when the CinGel/CinAlg mass ratio was 7:3. On SEM photographs, some spray-dried CinGel/CinAlg particles were spherical and others were irregularly shaped, and the diameter was a few to tens of micrometers. The release degrees of amaranth loaded in UV-treated microparticles were lower than those of the dye loaded in UV-untreated ones, possibly because of the photo cross-linkage of CinGel and CinAlg. Regardless of whether the microparticles were UV-treated, the release degree at pH 4.0 was significantly lower than the release degree at pH 6.0 and pH 8.0, possibly because of complexation of CinGel and CinAlg under the acidic condition.     

Effect of tris(hydroxymethyl) aminomethane on the phase behavior of poly(ethylene imine)/cinnamic acid conjugate and the release property of cubic phase containing the conjugate

The upper critical solution temperature (UCST) of poly(ethylene imine)/cinnamic acid (PEI/CA) conjugate decreased as the tris(hydroxymethyl) aminomethane (THMAM) concentration increased. On the optical micrographs of PEI/CA mixture solutions at 25°C, the microspheres were found when the THMAM concentration was 0?mM and 100?mM, but hardly found at 200?mM. Monoolein (MO) cubic phase containing PEI, CA, and THMAM exhibited a bilayer structure on the TEM micrograph. The release degree of methylene blue loaded in the cubic phase was not strongly dependent on THMAM concentration at 25°C and 37°C, but strongly dependent on the concentration at 50°C.     

Monoolein cubic phase containing disulfide proteinoid and its reduction-responsive release property

Monoolein (MO) cubic phase, which can release its payload in answering to reducing condition, was prepared by including a disulfide proteinoid composed of Asp, DL-leucine (Leu), and dithiodipropionic acid (DTPA) in its water channel. On the TEM micrograph, the cubic phase could accommodate the proteinoid with no change in its bilayer structure. The phase transition temperature of the cubic phase was about 58.7°C, and it was little affected by the proteinoid. The release degree of allura red loaded in the cubic phase was higher at a higher dithiothreitol (DTT) concentration. The proteinoid would be broken down by the reducing agent, facilitating the release.     

Low-pH-induced transformation of bilayer membrane into bicontinuous cubic phase in dioleoylphosphatidylserine/monoolein membranes

Cubic biomembranes, nonbilayer membranes with connections in three-dimensional space that have a cubic symmetry, have been observed in various cells. Interconversion between the bilayer liquid-crystalline (L(alpha)) phase and cubic phases attracted much attention in terms of both biological and physicochemical aspects. Herein we report the pH effect on the phase and structure of dioleoylphosphatidylserine (DOPS)/monoolein (MO) membranes under a physiological ion concentration condition, which was revealed by small-angle X-ray scattering (SAXS) measurement. At neutral pH, DOPS/MO membranes containing high concentrations of DOPS were in the L(alpha) phase. First, the pH effect on the phase and structure of the multilamellar vesicles (MLVs) of the DOPS/MO membranes preformed at neutral pH was investigated by adding various low-pH buffers into the MLV suspension. For 20%-DOPS/80%-MO MLVs, at and below pH 2.9, a transition from the L(alpha) to cubic (Q(224)) phase occurred within 1 h. This phase transition was reversible; a subsequent increase in pH to a neutral one in the membrane suspension transformed the cubic phase into the original L(alpha) phase. Second, we found that a decrease in pH transformed large unilamellar vesicles of DOPS/MO membranes into the cubic phase under similar conditions. We have proposed the mechanism of the low-pH-induced phase transition and also made a quantitative analysis on the critical pH of the phase transition. This finding is the first demonstration that a change in pH can induce a reversible phase transition between the L(alpha) and cubic phases of lipid membranes within 1 h.     

In Vitro Skin Permeation Enhancement of KIOM-MA-128 by Monoolein Cubosomes

Monoolein (MO) cubosomes were investigated in terms of in vitro skin permeation enhancer of KIOM-MA-128 (MA-128), a natural product known to be efficacious against atopic dermatitis. First, an aqueous suspension of MA-128 was prepared by homogenizing the powder in Pluronic F-127 (a dispersant) solution in water. The Pluronic F-127 concentration and the pH have no significant effect on the size and the zeta potential of MA-128 particles. The mean diameters and the zeta potentials fell within 1000–1500 nm and ?10 to ?20 mV, respectively. The sedimentation rate of the particles was lower at a higher concentration of the polymeric dispersant, possibly because the polymeric surfactant can act as a spring and push away approaching particles. The size of MO cubosomes was tens to hundreds of nanometers and exhibited black and white stripes. Cumulative amount of MA-128 permeated through hairless mouse skin was obviously higher when the cubosome was included in the MA-128 suspensions. However, the cumulative permeation amount was inversely proportional to the content of cubosomes, when the contents of cubosome in the suspension increased from 0.5% to 2.0% with MA-128 concentrations kept constant (2%).     

pH‐triggerable and ultraviolet‐triggerable β‐cyclodextrin microgel

β‐Cyclodextrin (βCD) microgels were prepared water in oil emulsion, and cinnamic acid (CA) was loaded in the microgel by inclusion complexation. The specific loading of CA in the microgel was 0.0203 mg/mg, and it was less than that the calculated specific loading (0.0368 mg/mg). The maximum swelling ratio of CA‐loaded βCD microgel (CAβCD microgel) decreased from 233.9% to 225.7% upon the irradiation of ultraviolet light (λ = 365 nm). And the 5(6)‐carboxyfluorescein release of CAβCD microgel, observed for 12 h, was suppressed upon the irradiation of ultraviolet light, possibly because the microgel can be photocross‐linked, and its mass transfer resistance against dye diffusion would increase. The swelling ratio of CAβCD microgel somewhat depended on the pH value of the medium, possibly because electrostatic repulsion can be developed within the microgel by the ionizable carboxylic group of CA. The 5(6)‐carboxyfluorescein release degree in 12 h of CAβCD microgel increased from 10.5% to 85.1% when the pH value increased from 3.0 to pH 9.0. This is mainly because CA is more soluble at a higher pH value. In the full range of pH value tested, the release degrees of CAβCD microgel were slightly higher than those of βCD microgel, possibly because of the electrostatic repulsion developed within the CAβCD microgel. Copyright © 2014 John Wiley & Sons, Ltd.     

Aqueous self-assembly of phytantriol in ternary systems: effect of monoolein, distearoylphosphatidylglycerol and three water-miscible solvents

The aqueous phase behavior of phytantriol (PT) in mixtures of monoolein (MO), distearoylphosphatidylglycerol (DSPG), propylene glycol (PG), polyethylene glycol 400 (PEG 400) and 2-methyl-2,4-pentanediol (MPD) was investigated by visual inspection, polarized light microscopy and small angle X-ray diffraction at room temperature. The phase diagrams of PT and MO in water are qualitatively very similar and PT/MO mixtures in excess water form one cubic phase of space group Pn3m irrespective of mixing ratio. The addition of the charged membrane lipid DSPG to the PT system gives rise to a considerable water swelling of the cubic phases as well as the occurrence of a cubic phase of space group Im3m. Whereas all three solvents studied give rise to a sponge (L3) phase in the MO-water system, this phase was only found when MPD was added to the PT-water system. The results are discussed with respect to the chemical differences between PT and MO.     

SAXS investigation of a cubic to a sponge (L3) phase transition in self-assembled lipid nanocarriers

The encapsulation and release of peptides, proteins, nucleic acids, and drugs in nanostructured lipid carriers depend on the type of the self-assembled liquid-crystalline organization and the structural dimensions of the aqueous and membraneous compartments, which can be tuned by the multicomponent composition of the systems. In this work, small-angle X-ray scattering (SAXS) investigation is performed on the 'melting' transition of the bicontinuous double diamond cubic phase, formed by pure glycerol monooleate (MO), upon progressive inclusion of varying fractions of pharmaceutical-grade glycerol monooleate (GO) in the hydrated system. The self-assembled MO/GO mixtures are found to form diamond (Pn3m) inverted cubic, inverted hexagonal (H(II)), and sponge (L(3)) phases at ambient temperature in excess of aqueous medium without heat treatment. Mixing of the inverted-cubic-phase-forming MO and the sponge-phase-forming GO components, in equivalent proportions (50/50 w/w), yields an inverted hexagonal (H(II)) phase nanostructured carrier. Scattering models are applied for fitting of the experimental SAXS patterns and identification of the structural changes in the aqueous and lipid bilayer subcompartments. The possibility of transforming, at ambient temperature (20 °C), the bicontinuous cubic nanostructures into inverted hexagonal (H(II)) or sponge (L(3)) mesophases may facilitate novel biomedical applications of the investigated liquid crystalline self-assemblies.     

聚邻氨基酚/Ni2+修饰碳糊电极的制备及其对葡萄糖的电催化氧化

以循环伏安法在碳糊电极(CPE)表面上修饰聚邻氨基酚膜(P-OAP),再以浸泡吸附法在此膜中嵌入金属离子Ni2 ,制成Ni/P-OAP/CPE。该电极在0.09mol/LNaOH溶液中通过90圈扫描活化后,在-0.15至0.65V区间出现一对峰形良好且稳定的氧化还原峰。循环伏安实验发现,Ni/P-OAP/CPE对葡萄糖的电氧化有良好的催化特性,催化活性受薄膜的厚度、薄膜中Ni2 的浓度、电极的活化时间以及电解液组成的影响。实验结果表明:该电极是一种良好的无酶葡萄糖传感器。     

高镁含硼盐卤体系反常现象解析

高镁含硼盐卤体系中存在"过饱和溶解度"、"稀释成盐"和同名离子"增溶"等反常现象。研究发现:氯化镁溶液在中低浓度时显中性,在高浓度时显酸性,饱和时pH值小于4.5。而各种镁硼酸盐基本都是pH值大于8.0的碱性矿物。水溶液中酸碱难共存,但镁硼酸盐与氯化镁却因具有相同离子而能够在高镁含硼盐卤体系中共存。结合氯化镁溶液特殊酸度变化规律与相关相化学数据可较圆满的解释高镁含硼盐卤体系中的反常现象。