Medicine and Health Sciences Commons^™

Self-Emulsified Nanoemulsion As Permeation Enhancer And Its Application For Intranasal Delivery Of Insulin, Kanyaphat Bunchongprasert

Theses and Dissertations

This study aimed to investigate the permeation enhancing property and safety of self-emulsified nanoemulsion (SEN) and use these findings to enhance insulin absorption through the nasal route.

The first part of the project was to identify the factors affecting cytotoxicity and permeation enhancement of SEN on Madin-Darby Canine Kidney (MDCK) cells, a widely used paracellular model. Twenty-six fatty acid esters (FAEs) commonly used in SEN were investigated. Among the FAEs (mono-, di-, and triesters), fatty acid monoesters (FAME) are the main excipient causing cytotoxicity and opening tight junction. The cytotoxicity of FAME in SEN was reduced with the presence of …

Targeting The Rage Signaling Pathway To Ameliorate The Complications Of Diabetes, Stephen James Dansereau

Legacy Theses & Dissertations (2009 - 2024)

Diabetes is a global health epidemic that can be devastating to those afflicted,

Trends In Prices Of Insulin Marketed In The Us, Hana Althobaiti

Pharmaceutical Sciences (MS) Theses

INTRODUCTION: Diabetes mellitus is one of the most prevalent and costly chronic diseases in the United States (US). The healthcare and drug cost of diabetes has risen steadily and the increase in patients’ out-of-pocket drug expenditures are associated with a reduction in treatment adherence. The objectives of this study were to assess trends in insulin products prices in the period January 1983-July 2019, and to compare the price, acquisition costs and reimbursement amount of insulins available in the US.

DATA AND METHODS: Data of insulin products marketed in the US during the period January 1983-July 2019 was derived from the …

Injectable Systems For Long-Lasting Insulin Therapy, Kumar Kulldeep Niloy

Theses and Dissertations (ETD)

Diabetes mellitus is one of the major global health problems and the prevalence rate is ever increasing reaching to 48% increase by the year of 2040 causing significant economic burdens. Insulin therapy has been the mainstay of diabetes treatment since its discovery in 1922. However, insulin is an unstable peptide with a half-life of only 4-6 min which poses significant challenge in prolonging duration of action of insulin. Nevertheless, the advances in recombinant DNA technology and protein engineering have enabled the development of several long-acting insulin analogue products which show duration of action up to 42 h. However, these insulin …

Intranasal Delivery Of Insulin By Nanoemulsion System, Darshana Mahendrakumar Shah

Theses and Dissertations

The main objective of this research was to develop an o/w nanoemulsion dosage form of insulin for intranasal delivery where insulin is loaded into the oil phase of the nanoemulsion for enhanced absorption. When loaded into the lipid droplets (oil phase), insulin can be protected from enzymatic degradation, can permeate through the mucus gel barrier in a comparatively efficient manner and can be absorbed through transcellular permeation along with paracellular route. To incorporate lipophilicity to insulin molecule, several complexes of insulin with various amphiphiles were developed to load it into the oil phase. The cytotoxicity of these amphiphiles and the …

A1c Reduction And Weight Loss In A Veteran Population Using Glp-1-Ras, Shelby L. Beutel Darrow

Undergraduate Honors Thesis Collection

Background: Diabetes mellitus is a metabolic disorder defined by high blood glucose. Glucagon-like peptide-1 receptor agonists (GLP-1-RAs) are a newer class of medications that offer potential 2 to 3 kg weight loss and a 1% to 1.5% decrease in A1c. At the Indianapolis Veterans Affairs Medical Center (VAMC), GLP-1-RAs are non-formulary.

Objectives: Primary outcomes included mean change in weight, body mass index (BMI) and A1c in VAMC patients. Secondary outcomes included the comparison to published values, analysis of insulin needs, and analysis of GLP-1-RA discontinuation reasons.

Methods: Indianapolis VAMC patients ages 18-80 with type 2 diabetes who started a GLP-1-RA …

Insulin Actions On Hippocampal Neurons, Shaniya Maimaiti

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aging is the main risk factor for cognitive decline. The hippocampus, a brain region critical for learning and memory formation, is especially vulnerable to normal and pathological age-related cognitive decline. Dysregulation of both insulin and intracellular Ca2+ signaling appear to coexist and their compromised actions may synergistically contribute to neuronal dysfunction with aging. This dissertation focused on the interaction between insulin, Ca2+ dysregulation, and cognition in hippocampal neurons by examining the contributions of insulin to Ca2+ signaling events that influence memory formation. I tested the hypothesis that insulin would increase cognition in aged animals by altering Ca2+-dependent physiological mechanisms involved …

The Influence Of Antidiabetic Medications On The Development And Progression Of Prostate Cancer, Anna Elizabeth Hitron

University of Kentucky Master's Theses

The development of prostate tumors has been linked to co-morbid diabetes mellitus (DM) in several studies, potentially through the stimulation of insulin-like growth factor receptor (IGFR). This study evaluates the effect of anti-diabetic medication use on the development of high grade tumors and time to tumor progression compared to non-diabetics. This retrospective, nested case control study identified patients with prostate cancer (PCa) from the Kentucky Medicaid Database. Cases were diagnosed with PCa and DM and using at least one of the following antidiabetic medications; sulfonylureas, insulin, metformin or TZDs. Cases were further stratified on their insulin exposure resulting from therapy. …

Controlled Release Of Insulin And Modified Insulin From A Novel Injectable Biodegradable Gel, Om Anand

Theses and Dissertations (ETD)

The objective of the study was to develop a controlled release dosage form of
insulin, which can provide basal concentrations of insulin in diabetic rats for 1 to 2 weeks after a single subcutaneous injection.
A biodegradable injectable drug delivery gel was prepared by dissolving a
biodegradable polymer, polylactic-co-glycolic acid (PLGA), in biocompatible
plasticizer(s), triethyl citrate (TEC) and/or acetyl triethyl citrate (ATEC). Insulin was
then loaded into the blank gel to form an insulin suspension in the polymer solution.
After the insulin-loaded gel was injected subcutaneously, the plasticizer(s) dissolved in the aqueous media and were gradually taken away from the …

Selective Regulation Of Cardiomyocyte Signaling By Rgl2, Leah M. Allen

University of Kentucky Doctoral Dissertations

A key cardiovascular signaling molecule involved in both physiologic and pathologic regulation of cardiomyocytes is the small molecular weight G-protein, Ras. Differential effects of Ras are mediated by multiple effector molecules, including the RalGEFs which activate Ral. Studies performed in cardiomyocytes have indicated a role for Ral in cardiac hypertrophic signaling and the RalGEF family member, Rgl2, was shown to specifically interact with Ras in the heart. Therefore, I hypothesized that Rgl2 was an important Ras effector that would regulate cardiomyocyte signaling.

To elucidate the potential importance of Rgl2 in regulating cardiomyocyte signaling, a gain-of-function approach was utilized in which …

Alterations In Calcium Homeostasis And The Insulin-Like Growth Factor Signaling Pathway Induced By Carcinogenic Polycyclic And Halogenated Aromatic Hydrocarbons In Human Mammary Epithelial Cells, Stacey L. Tannheimer

Pharmaceutical Sciences ETDs

Breast cancer is a major health concern for women, with only a small percent of the risk factors currently identified. It has been estimated that environmental factors may contribute to up to 80% of breast cancer cases. Many environmental carcinogens, such as polycyclic and halogenated aromatic hydrocarbons (PAHs and HAHs), are proven mammary carcinogens in animal models. Therefore, these studies were conducted to elucidate potential roles of PAHs and HAHs in alterations in known signaling pathways in human mammary epithelial cells (HMEC). Carcinogenic PAHs have previously been shown to produce sustained alterations in the calcium (Ca2') homeostasis of lymphocytes Therefore, …

Insulin Adsorption To Intravenous Delivery Systems, Michael Joseph Zarcone

University of the Pacific Theses and Dissertations

Lack of quantitative adsorption data makes it difficult for a physician to determine the actual amount of insulin received by a patient against the amount added to the intravenous infusion system. This project was therefore initiated to determine quantitatively the extent of adsorption that would occur in a clinical setting.

In order to achieve the above aim, varying amounts of carrier insulin containing I-labeled insulin were added to the intravenous infusion delivery system. Using the most commonly utilized mode of delivery and flow rate the tagged insulin solution was allowed to flow through the intravenous delivery system. Both the amount …