Physicochemical studies basic to cholesterol gallstone formation and dissolution: correlation between cholesterol thermodynamic activity laser light scattering data nucleation times and or dissolution tendencies.

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Title Physicochemical studies basic to cholesterol gallstone formation and dissolution: correlation between cholesterol thermodynamic activity laser light scattering data nucleation times and or dissolution tendencies.
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Liu, Chen-Lun.
Contributor Jain, Uday K. Dr.; Lee, Paul H. Dr.
Date 1993-06
Description An improved silicone polymer uptake method for measuring cholesterol (Ch) thermodynamic activity (AT) was employed in studying supersaturated model bile systems. The method permits rapid determination of AT and thus avoids the possible complications resulting from Ch crystal nucleation. Several different approaches to incorporate positive charges onto the surface of a thin silicone polymer film resulted in reducing the equilibrium time from 12-24 hours to 1-2 hours. Quasielastic light scattering (QLS) was used to investigate the sizes and polydispersity for micelles, vesicles, and crystals in the Ch-bile salt (BS)-lecithin (L) solutions. Based on the AT data, time dependent measurements were focused on supersaturated Ch concentrations at different BS:L ratios. Further, the relationship between Ch nucleation times and AT was studied over a wide range of supersaturated biles. The results show that, when vesicles were present, the Ch nucleation times were nearly the same under the same AT regardless of the type of BS, the BS:L molar ratio, the total lipid concentration, or the nucleating promoters (i.e., Ca+2). These results suggest that AT is an important factor in explaining Ch monohydrate nucleation tendencies in model biles. However, when vesicles were absent, the supersaturated bile remained kinetically stable (i.e., no nucleation) up to 50 days, even though their AT values were high enough to cause rapid nucleation when mesophase was present. These further prove that AT rather than supersaturation is the driving force and the vesicles are catalytic in the Ch nucleation process. In parallel, a detailed QLS study of pure tauroursodeoxycholate (TUDC)-L-Ch solutions and pure taurochenodeoxycholate (TCDC)-L-Ch solutions was also conducted. In the TUDC-L-Ch case, vesicles dominated the scattering at AT ~ 0.6. Based on measurements of the total scattered light intensity, the vesicles represented only a small fraction of the total lipid concentration (< 3%) even at the highest Ch concentrations studied. In contrast, the TCDC-L-Ch system demonstrated only micelles up to unit AT. A novel quantitative model of the AT data indicates that TUDC-L mixed micelles bind Ch in a highly cooperative multisite process, whereas TCDC-L mixed micelles exhibit much less cooperativity. Further, a thermodynamic model of vesicle formation, that accounts for the differences between the TUDC-L-Ch and TCDC-L-Ch systems in terms of the activities of L and Ch corresponding to each system, is also presented.
Type Text
Publisher University of Utah
Subject Biocmedial Research; Pharmacology
Subject MESH Cholelithiasis; Cholesterol
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Physicochemical studies basic to cholesterol gallstone formation and dissolution: correlation between cholesterol thermodynamic activity laser light scattering data nucleation times and or dissolution tendencies." Spencer S. Eccles Health Sciences Library. Print version of "Physicochemical studies basic to cholesterol gallstone formation and dissolution: correlation between cholesterol thermodynamic activity laser light scattering data nucleation times and or dissolution tendencies." available at J. Willard Marriott Library Special Collection.
Rights Management © Chen-Lun Liu.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,3
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship Naational Institute of Health.
ARK ark:/87278/s6154xp6
Setname ir_etd
ID 193979
Reference URL https://collections.lib.utah.edu/ark:/87278/s6154xp6
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