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The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (p<0.05) in the chemoresistant cells in both MTT and colony formation assays. Hence, this new ATRA-nanoformulation may offer promising means for the delivery of lipophilic compounds like all-trans retinoic acid to treat highly resistant ovarian cancer. / Pharmaceutical Sciences

Macrophages can be activated by a variety of extracellular signals to polarize to either the M1 (inflammatory and antimicrobial) or to the M2 (wound repair and inflammation resolution) phenotype. Expression of arginase 1 in macrophages is a key marker of the M2 phenotype. Arginase 1 expression is induced by interleukin 4 (IL-4), a cytokine secreted by Th2 helper cells. All-trans retinoic acid (ATRA) is a product of metabolism of dietary retinol (vitamin A). In a manner analogous to hormones, ATRA binds to nuclear receptors in cells and influences gene expression and cell physiology. ATRA is important in the resolution of inflammation systemically and on the cellular level, however it has not been linked to M2 activation or arginase 1 expression. Testing the hypothesis that ATRA can induce arginase 1 in macrophages either directly or indirectly, it was found that ATRA alone cannot cause murine bone marrow-derived macrophages (BMDM) to activate in the M2 phenotype (as indicated by arginase 1 expression), however it can dramatically potentiate induction of arginase 1 expression and activity by IL-4. This is the first observation positively linking ATRA to arginase 1. Lipopolysaccharide (LPS), is a conserved structural component of the outer membrane of Gram negative bacteria, and a potent pyrogen. In metabolic endotoxemia, LPS concentration in the blood is slightly elevated, and over the long term this contributes to diverse inflammatory diseases such as atherosclerosis, obesity, and diabetes. LPS promotes the M1 phenotype and suppresses the M2 phenotype, but its contribution at low doses such as those found in metabolic endotoxemia are not well studied. In order to investigate mechanisms of LPS suppression at low doses, mice deficient in IRAK1 and tollip, key mediators or proinflammatory LPS signaling, were used to study IL-4, ATRA, and LPS crosstalk. LPS suppression of arginase 1 was found to be dependent on IRAK1 and tollip, but only at low doses of LPS. / Ph. D.

This qualitative study reflects the researcher's aim to capture the oral histories of students who attended Lee M. Waid, an all-Black rural Virginian school, between 1963 and 1970. This purpose lies in the researcher's attempt to thoroughly and accurately capture a time in history after desegregation was mandated, Freedom of Choice plans were implemented or being created, and integration was occurring across the nation, Virginia, and Franklin County. This study is guided by the research question: What were the experiences of students and staff who were part of Lee M. Waid School during the years 1963 to 1970? The researcher followed the 10-step interview protocol of Creswell and Poth (2018) and adapted 15 interview questions from Johnson's (2015) dissertation The Addisonians: The Experiences of Graduates of the Classes of 1963-70 of Lucy Addison High School, An All-Black High School in Roanoke, Virginia. The interview questions were slightly adapted to suit the researcher's study to gain insight about student experiences at Waid School. The researcher purposefully selected 14 participants by looking at existing data through the use of primary documents and snowball or chain methodology. Fourteen of the participants were former students of Waid School and two were former faculty members of Franklin County Public Schools. The exploration of student experiences during desegregation is vital to preserving the history, legacy, and influence of Black education. / Doctor of Education / The purpose of this study was to shed light on the experiences of Black students during desegregation in Franklin County, Virginia. The researcher aimed to capture the oral histories of students who attended Lee M. Waid, an all-Black rural Virginian school, between 1963 and 1970. The voices of the participants and their stories add to the breadth of literature and body of knowledge on the desegregation process. Before the completion of this study, the perspectives and experiences of participants had not been formally documented. A brief review of the literature on the history of Black education at the national, state, and local levels provides essential background information for historical context leading to the desegregation of United States public schools. An overview of southern segregated schools provides insight into the supports and values held within all-Black schools before and after the initiation of the desegregation of schools. The examination of student experiences during desegregation provides critical insight on America's pathway toward equity in education, the effect of desegregation from the student perspective, and the remnants of segregation that still exist today in American public schools. Through a qualitative case study, the researcher conducted interviews with former students and stakeholders of Lee M. Waid. The researcher reviewed primary documents such as yearbooks, newspaper articles, and other documents provided by participants. Through interviews with participants, (a) high expectations from teachers and administrators, (b) parent and community support, (c) familial attitudes or beliefs about segregation and integration, (d) school pride, and (e) each participant meaningfully reflected on their individual school experiences during desegregation. The themes identified in the study are similar to those identified by other researchers who have explored the initial desegregation of schools and the supports and values held within segregated schools. One of the recommendations of this study encourages additional research and documentation of student experiences during desegregation. The exploration of student experiences during desegregation is vital to preserving the history, legacy, and influence of Black education.