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2. Development of the cholestosome, a novel delivery system made exclusively from cholesteryl esters.

Author

Mielnicki, Lawrence, Hughes, Julie, Schentag, Jerome, Irving, Mary, Monetti, Victoria, Fraser MacArthur, John, Cordone, David, and McCourt, Mary

Subjects
ORGANIC solvents, ALZHEIMER'S disease, ESTERS, LATENT infection, DRUG delivery systems, BILE salts
Abstract

A novel vesicular drug delivery system has been created using only cholesteryl esters. The uncharged nature of the esters requires a formulation process that uses energy, in the form of sonication, to facilitate the cholesteryl esters formation into vesicles. The nature of the material choices renders the vesicles resistant to pH degradation between a pH of 2 and 10. Storage condition at 4°C for 9 months shows a stability of encapsulated materials as well as vesicles. The formulation process is a modified reverse phase method in which the esters are dissolved in an organic solvent, which is then removed and the aqueous component is then added with sonication in a temperature‐controlled water bath. A wide variety of materials can be encapsulated in these vesicles, which are called cholestosomes. Delivery of the cholestosome‐encapsulated materials is a function of the ester component structure and not the encapsulated molecule. Once encapsulated, the vesicles deliver the materials into cells. The potential for oral availability was explored using chylomicrons. Successful delivery of the cholestosome encapsulated into chylomicrons has enhanced the effectiveness of delivery to cells. Analytical methods have been developed to analyze the materials chosen from the cholesteryl esters as well as the encapsulated materials. Practical Applications: The creation of the cholestosome vesicle opens up completely new areas for encapsulating and delivering materials. The cholesteryl ester structure that makes up the vesicles is impervious to pH and bile salts, making cholestosomes ideal for oral delivery of drugs, such as oral insulin. Intracellular delivery of cholestosome vesicles enables multiple applications, from killing latent infections to preventing viral replication (irrespective of the virus) and delivering nucleic acid therapeutics to cure genetic disease. These vesicles pass the blood–brain barrier and could be used for treatments of Alzheimer's and related neurodegenerative disease. Cholestosomes can also be used in cosmetic formulations as the vesicles pass the dermis. They even could be used in food applications as the materials are considered generally regarded as safe. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Advocates of the Peace, A Qualitative Study of Former Politically Motivated Female Prisoners and Conflict Resolution in Northern Ireland

Author

McCourt, Mary and Dr. Mary Rogan

Subjects
Conflict Resolution, The Good Friday Agreement, Women, Northern Ireland, Social and Behavioral Sciences
Abstract

The Good Friday Agreement is extensively recognised and acknowledged as a successful model of conflict resolution. Prior to its implementation and in the aftermath of the agreement, former politically motivated female prisoners have been instrumental in securing support for the agreement and also sustaining the agreement in the grassroots communities in Northern Ireland. This study explores the roles in which former politically motivated female prisoners have undertaken in micro levels of conflict resolution and presents a gendered perspective of conflict resolution. Findings within this study reveal the grassroots activities of participants, which is aligned with preventing violence within interface communities in Northern Ireland. One of the main findings within the study point to the credibility of the participants as former politically motivated prisoners as being instrumental in their roles

Published
2013

6. Computational Analysis of the Apoptotic Activity of a Small Library of Novel Substituted Hydroxy Ureas Designed as Potential Inhibitors of Ribonucleotide Reductase

Author

P. McCourt, Mary, primary, S. Greene, Robert, additional, Smith, Charles, additional, McClory, Haley, additional, Wirth, Christopher, additional, Sumbler, Brittany, additional, L. Emery, Michelle, additional, D. Leskiw, Brian, additional, G. Krause, Josef, additional, E. McGahan, Megan, additional, Vanio, Shawn, additional, Jordan, Michael, additional, Pericozzi, Angela, additional, and Priefer, Ronny, additional

Published
2011
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19. Electron Crystallographic Analysis of a Polysaccharide Structure—Direct Phase Determination and Model Refinement for Mannan I

Author

Dorset, Douglas L. and McCourt, Mary P.

Abstract

Three-dimensional electron diffraction intensity data from the polysaccharide mannan I, previously published by H. Chanzy et al. (1987; Macromolecules 20, 2407-2413), were used for an ab initio structure determination. The space group is P212121, with unit cell constants a = 8.92, b = 7.21, c = 10.27 Å. After determination of crystallographic phases by evaluation of triplet and quartet structure invariants, 41 values were assigned to 58 unique reflections, 11 linked through a single algebraic unknown a. Two potential maps corresponding to two possible values of a were calculated by a Fourier transformation of the limited 3D data set, combining the phase terms with measured structure factor magnitudes. Either map allowed a monomer model, taken from the crystal structure of methyl α-d-mannopyranoside, to be fit very well in the xy plane, since 24 of 34 hk0 data are accessed by the direct phase determination. Although the limited goniometer tilt range is responsible for an incomplete sampling of the 3D reciprocal net, resulting in a series termination effect, a choice could be made between the two possible maps (permuting the unknown phase term a = ±π/2), since only one is a good envelope to the monomer structure in the chain direction. After optimizing linkage geometry, a structure that is very close to the initial determination was derived based on a conformational refinement. Copyright 1993, 1999 Academic Press

Published
1993
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25. Comparison of the active site interactions of two lipophilic adamantyl antifolates with bacterial and avian dihydrofolate reductase

Author

McCourt, Mary and Cody, Vivian

Subjects
Binding sites (Biochemistry) -- Research, Dihydrofolate reductase -- Physiological aspects, Enzyme inhibitors -- Physiological aspects, Business, Health care industry
Abstract

AUTHORS: Mary McCourt and Vivian Cody. Medical Foundation of Buffalo, Buffalo, New York. According to the author's abstract of a presentation to the 81st annual meeting of the American Association [...]

Published
1990

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