This diploma thesis was focused on the system of agarose hydrogels with micellar domains. Polysaccharide agarose was used for the preparation of hydrogel matrices. Septonex was chosen as a surfactant. The release of solubilizate from the agarose hydrogel matrix was studied with a hydrophobic dye Sudan III in order to obtain a model system of hydrophobic solubilized drugs. Sudan III was solubilized via surfactant´s micels. Subsequently, this micellar aqueous solution with the dissolved dye was used to prepare the agarose hydrogel. The system was prepared in the environment of deionized water and physiologic solution. The gradual release of the dye into deionized water and physiologic solution was studied for 22 days using the UV-VIS spectrophotometry method. It was found that after 14 days the concentration of the releasing dyes into the deionized water was decreased. The cause is that after 14 and 22 days there was a slight degradation of gels, which was detected using the rheology method. Using the rheology method it was also found that Septonex does not affect the gel formation process.

Surfactants self-assemble into aggregates above a certain concentration. In this work mixtures of the cationic surfactant cetyltrimetylammonium bromide (CTAB) and the anionic surfactant sodium octyl sulfate (SOS) were investigated systematically. The measurements were accomplished by combining the two complimentary techniques static light scattering (SLS) and cryo-transmission electron microscopy (CRYO-TEM). It was found that CTAB-rich samples contain large threadlike micelles rather close to mole fractions where vesicles start to form. The mole fraction x of the surfactant in excess in the aggregates was calculated and it was found that it differs a lot from the mole fraction in the bulk, and the transition from micelles to vesicles occurs when x is about 0.7. In the SOS-rich samples small globular micelles were observed that transform into vesicles upon dilution. Some of the samples rich in SOS were found to contain open vesicles with CRYO-TEM and the reasons for this behavior have been discussed. One question that needs to be further investigated is whether or not these structures are the result of some kind of distortion of the equilibrium process during sample preparation in connection with CRYO-TEM measurements. In most cases the two methods showed consistent results and trends, but for some samples differences could be observed.

Background: Near-IR fluorescence (NIRF) imaging is becoming a promising approach in preclinical tumor detection and clinical image-guided oncological surgery. While heptamethine cyanine dye IR780 has excellent tumor targeting and imaging potential, its hydrophobic property limits its clinical use. In this study, we developed nanoparticle formulations to facilitate the use of IR780 for fluorescent imaging of malignant brain tumor. Methods: Self-assembled IR780-liposomes and IR780-phospholipid micelles were prepared and their NIRF properties were characterized. The intracellular accumulation of IR780-nanoparticles in glioma cells were determined using confocal microscopy. The in vivo brain tumor targeting and NIRF imaging capacity of IR780-nanoparticles were evaluated using U87MG glioma ectopic and orthotopic xenograft models and a spontaneous glioma mouse model driven by RAS/RTK activation. Results: The loading of IR780 into liposomes or phospholipid micelles was efficient. The particle diameter of IR780-liposomes and IR780-phospholipid micelles were 95 and 26nm, respectively. While stock solutions of each preparation were maintained at ready-to-use condition, the IR780-phospholipid micelles were more stable. In tissue culture cells, IR780-nanoparticles prepared by either method accumulated in mitochondria, however, in animals the IR780-phospholipid micelles showed enhanced intra-tumoral accumulation in U87MG ectopic tumors. Moreover, IR780-phospholipid micelles also showed preferred intracranial tumor accumulation and potent NIRF signal intensity in glioma orthotopic models at a real-time, non-invasive manner. Conclusion: The IR780-phospholipid micelles demonstrated tumor-specific NIRF imaging capacity in glioma preclinical mouse models, providing great potential for clinical imaging and image-guided surgery of brain tumors.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23222号 / 工博第4866号 / 新制||工||1759(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 秋吉 一成, 教授 大内 誠, 准教授 松岡 秀樹 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

This project deals with the mixed micellar and interfacial properties of mixtures of three surfactants [sodium dodecyl sulphate (SDS), cetyltrimethylammonium bromide (CTAB), and tetraethylene glycol monododecyl ether (C12E4)] with ABA symmetrical triblock copolymer (Pluronic F127), which has many industrial applications. Evidence of F127 micellisation and interaction with surfactants in the aqueous phase is inferred through interfacial tension measurements. The solution containing diluted monomeric F127 showed complex formation with surfactants before the latter self-aggregate as pure micelles. The simultaneous presence of ionic surfactants and micellar F127 in solutions displayed a decrease of interfacial activity and led to the conclusion of F127 micelles disruption. C12E4 was found to interact differently with micellar F127 in forming mixed micelles, and no loss of interfacial activity was recorded. This “association-dissociation” behaviour of F127 and surfactants was leveraged to understand the stability of mineral oil in water emulsions formulated with them in the presence of sodium phosphate (Na3PO4). The mechanisms of emulsions breakdown were found to rely on aggregation behaviour and complex structure of F127 and surfactants mixtures in solution. Laser diffraction showed that unlike SDS and CTAB, mixed-emulsifier systems containing C12E4 are stable to both flocculation, Ostwald ripening and coalescence. Due to electrostatic repulsion between its head group and F127 hydrophilic block, and also because of the combined effect of Ostwald ripening and coalescence, CTAB emulsifier containing systems displayed quicker instability than SDS. SDS containing systems showed a progressive shifting of droplets size distributions to bimodality as SDS concentration was increased and heat exposure pursued, revealing the activity of two distinct population of droplets in the emulsions. More insight on the mechanisms underlying the stability of the three mixed emulsifier systems was gained in performing optical microscopy and rheology measurements; the results were found to be consistent with particle size distribution. / Dissertation (MSc (Applied Science: Chemical Technology))--University of Pretoria, 2020. / Chemical Engineering / MSc (Applied Science: Chemical Technology) / Unrestricted

No description available.

The effect of ultra-high temperature processing by direct steam injection and room temperature storage of pH-adjusted and unadjusted 3X (volume reduction) skim milk retentate and the effect of storage at various temperatures of 3X skim milk retentate without pH adjustment on their ζ-potential, viscosity, and pH were determined. Pasteurized skim milk was concentrated to 3X by ultrafiltration. In the pH study portions of skim milk retentate were adjusted to pH 6.38 ± .02 with HCl and 6.85 ± .01 and 7.32 ± .02 with NaOH between ultrafiltration and ultra-high temperature processing. In the storage temperature study, storage temperatures used for pH-unadjusted retentate samples were 11°C, 23°C (room temperature), and 37°C. Although pH 6.38 samples had the lowest viscosity in the pH study before ultra-high temperature processing, these samples precipitated during ultra-high temperature processing. For non-acidified samples, increasing pH of retentate resulted in higher viscosities and quicker age gelation times. Destabilization occurred more rapidly at 37°C than at 23°C or 11°C. The pH drop tended to be greater for samples stored at a higher temperature or adjusted to a higher pH. During 28 weeks of 37°C storage the pH decreased from 6.54 to 6.06. During 32 weeks of 23°C storage pH of samples initially adjusted to pH 7.32 dropped to 7.06. ζ-Potentials of casein micelles were calculated from electrophoretic mobility obtained by measuring Doppler frequency shifts of scattered laser light in samples that had been diluted 300 fold with their own ultra.filtrate. Absolute values of ζ-potential of samples stored at 37°C decreased from -23.4 millivolts immediately after ultra-high temperature processing to -18.5 millivolts after 28 weeks of storage. For samples stored at 11°C and 23°C in the storage temperature study and control samples in the pH study, absolute values of ζ-potential decreased approximately 1.5 to 2.0 millivolts during 28 or 32 weeks of storage.

Effects of aqueous surfactant solutions upon cis/trans isomerization reactions of various N-alkyl-merocyanine dyes (II) were studied. Dramatic rate enhancements were found for all dyes in CTAB and SDS solutions above the CMC. CTAB solutions showed the greatest effect with some dye isomerizations catalyzed in excess of 1000-fold. Increases in either CTAB concentration or dye isomerization rates. N-methyl through N-pentyl dye isomerization rates were measured as a function of CTAB concentration and the data treated according to the pseudophase model for micellar catalysis. KS values ranged from 198 to 2000 M-1 for N-methyl to N-pentyl dyes, respectively. Micellar rate constants also increased as dye hydrophobicity was increased. Thermodynamic activation parameters were determined for N-methyl through N-hexylmerocyanine dyes in CTAB solutions. Rate enhancements in CTAB (above the CMC) relative to those in purely aqueous solutions were shown to be due to a substantial lowering of ΔH‡, for the various dyes. Increased CTAB concentrations of N-methyl dye solutions gave reaction rate increases resulting from a lowering of ΔS‡. In 0.054 M CTAB, increases in reaction rates with increased N-alkyl chain length were due to large increases ΔS‡ (from ca. 0 eu for N-methyl to 13 eu for N-hexyl). The data were discussed in terms of molecular interactions which can occur within the micellar solubilization sites.

No description available.

The viability of a drug delivery system which encapsulates chemotherapeutic drugs (Doxorubicin) in the hydrophobic core of polymeric micelles and triggers release by ultrasound application was investigated at an applied frequency of 500 kHz. The investigation also included elucidating the mechanism of drug release at 70 kHz, a frequency which had previously been shown to induce drug release. A fluorescence detection chamber was used to measure in vitro drug release from both Pluronic and stabilized micelles and a hydrophone was used to monitor bubble activity during the experiments. A threshold for release between 0.35 and 0.40 in mechanical index was found at 70 kHz and shown to correspond with the appearance of the subharmonic signal in the acoustic spectrum. Additionally, drug release was found to correlate with increase in subharmonic emission. No evidence of drug release or of the subharmonic signal was detected at 500 kHz. These findings confirmed the role of cavitation in ultrasonic drug release from micelles. A mathematical model of a bubble oscillator was solved to explore the differences in the behavior of a single 10 um bubble under 70 and 500 kHz ultrasound. The dynamics were found to be fundamentally different; the bubble follows a period-doubling route to chaos at 500 kHz and an intermittent route to chaos at 70 kHz. It was concluded that this type of "intermittent subharmonic" oscillation is associated with the apparent drug release. This research confirmed the central role of cavitation in ultrasonically-triggered drug delivery from micelles, established the importance of subharmonic bubble oscillations as an indicator, and expounded the key dynamic differences between 70 and 500 kHz ultrasonic cavitation.