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Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit 2020 Virginia Commonwealth University

Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit

Theses and Dissertations

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than …


Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya 2019 University of Nebraska Medical Center

Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya

Theses & Dissertations

This work presents research using the naturally available non- sulfated carbohydrate glycosaminoglycan hyaluronic acid (HA) for the synthesis of different chemical derivatives of HA for evaluation of binding kinetics with CD44 and P- selectin proteins for applications in fluorescence image-guided surgery. Chemical derivatives of HA such as deacetylated HA (deHA), sulfated HA (sHA), and deacetylated and sulfated HA (s-deHA) were synthesized by modulating sulfating and deacetylating reagents to alter binding specificities to CD44. Modified HA derivatives and CD44 biophysical interactions were assessed by fluorescence polarization. In silico techniques were also used to determine binding using molecular docking and MM-PBSA approaches. …


Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann 2019 University of Nebraska Medical Center

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …


Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina 2019 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations & Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …


Electrospun Fibers And Nanoparticles For The Prevention Of Sexually Transmitted Infections., Kevin Michael Tyo 2019 University of Louisville

Electrospun Fibers And Nanoparticles For The Prevention Of Sexually Transmitted Infections., Kevin Michael Tyo

Electronic Theses and Dissertations

Human immunodeficiency virus-1 (HIV-1) and herpes simplex virus 2 (HSV-2) affect hundreds of millions of people worldwide, with women disproportionately impacted by these infections. Currently, only oral pre-exposure prophylaxis (PrEP) is approved specifically for the prevention of HIV-1, but is challenged with adverse side effects associated with long-term use. Topical delivery platforms, such as gels and films, deliver agents directly to the female reproductive tract, but are limited in providing transient-release. The technology of polymeric electrospun fibers may serve as alternative topical delivery platform to the female reproductive tract. In these studies, we fabricated electrospun fibers comprised of different polymers …


Engineering Nanomaterials For Imaging And Therapy Of Bacteria And Biofilm-Associated Infections, Akash Gupta 2019 University of Massachusetts Amherst

Engineering Nanomaterials For Imaging And Therapy Of Bacteria And Biofilm-Associated Infections, Akash Gupta

Doctoral Dissertations

Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. The “superbug” risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that are highly resistant to available treatments. Synthetic macromolecules such as polymers and nanoparticles have emerged as promising antimicrobials. Moreover, ability to modulate nanomaterial interaction with bacterial cellular systems plays a pivotal role in improving the efficacy of the strategy. In the initial studies on engineering nanoparticle surface chemistry, I investigated the role played by surface ligands in determining the antimicrobial activity of the nanoparticles. In further study, …


Synthesizing Galactose Modified Polymeric Nanoparticles For Biofilm Inhibition Of Pseudomonas Aeruginosa, Tyler R. Flockton 2019 Rowan University

Synthesizing Galactose Modified Polymeric Nanoparticles For Biofilm Inhibition Of Pseudomonas Aeruginosa, Tyler R. Flockton

Theses and Dissertations

Treating patients with antibiotics is becoming harder with the increase in antibiotic resistance. This is due to the widespread antibiotic use in clinical and agricultural settings. With antibiotic resistance outpacing new drugs making it to the market, developing new options to treat bacterial infections is and will be important. We created sugar modified nanoparticles to inhibit the biofilm formation of Pseudomonas aeruginosa.

P. aeruginosa is a gram-negative opportunistic pathogen that infects its host that has a compromised immune system. This makes it one of the most significant bacterial infection in hospitals. P. aeruginosa uses biofilms as an attack mechanism …


Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly 2019 The Graduate Center, City University of New York

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …


Synthesis And Characterization Of Long-Acting Rilpivirine Prodrugs, James R. Hilaire 2019 University of Nebraska Medical Center

Synthesis And Characterization Of Long-Acting Rilpivirine Prodrugs, James R. Hilaire

Theses & Dissertations

Antiretroviral therapy (ART) requires lifelong daily dosing to suppress viral replication, restore or maintain immune function and improve quality of life. As an alternative, long-acting (LA) antiretrovirals (ARVs) aim to deliver therapeutic drug concentrations over an extended period, ultimately requiring monthly or even more extended dosing intervals. Specifically, the success of recent clinical trials examining LA cabotegravir and rilpivirine (CAB and RPV LA) highlight the advent of these novel HIV-1 therapeutics. Further optimization of LA dosage forms are required and rests upon improving dosing frequency, injection volumes and tissue distribution to viral compartments. To this end, we report the synthesis …


Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw 2019 Pittsburg State University

Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw

Electronic Theses & Dissertations

In this study, a hyperbranched polyester co-polymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-Tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols. The resulting polymers were purified using the solvent precipitation method and characterized using various chromatographic and spectroscopic methods including GPC, MALDI-TOF, and NMR. We have observed polymers with a molecular weight of 29,643 kDa and 33,996 kDa, which is ideal to be …


A Robust Delivery System For Rna Therapeutics, Suleyman Bozal 2019 University of Connecticut

A Robust Delivery System For Rna Therapeutics, Suleyman Bozal

University Scholar Projects

The field of RNA therapeutics is currently undergoing both transformation and expansion. Specifically, research in lipid nanoparticle (LNP) based RNA therapeutics is gaining significant traction. Other research into mechanisms of gene regulation and manipulation, including siRNA and the CRISPR/Cas9 system have demonstrated the potential of RNA-based disease treatment. This work identifies a delivery system which can regulate expression of green fluorescent protein (GFP) in human embryonic kidney cells (HEK293) stably expressing GFP.

Analysis of siRNA-induced gene knockdown demonstrates that the current siRNA-LNP formulation is equally as effective as a commercially available transfection reagent, Lipofectamine RNAiMAX (RNAiMAX), which is designed specifically …


A Robust Delivery System For Rna Therapeutics, Suleyman Bozal 2019 University of Connecticut

A Robust Delivery System For Rna Therapeutics, Suleyman Bozal

Honors Scholar Theses

The field of RNA therapeutics is currently undergoing both transformation and expansion. Specifically, research in lipid nanoparticle (LNP) based RNA therapeutics is gaining significant traction. Other research into mechanisms of gene regulation and manipulation, including siRNA and the CRISPR/Cas9 system have demonstrated the potential of RNA-based disease treatment. This work identifies a delivery system which can regulate expression of green fluorescent protein (GFP) in human embryonic kidney cells (HEK293) stably expressing GFP.

Analysis of siRNA-induced gene knockdown demonstrates that the current siRNA-LNP formulation is equally as effective as a commercially available transfection reagent, Lipofectamine RNAiMAX (RNAiMAX), which is designed specifically …


Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim 2019 University of Nebraska Medical Center

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …


Polymeric Chloroquine: Modifying An Old Drug To Make It A Little Sweeter, Richard Sleightholm 2019 University of Nebraska Medical Center

Polymeric Chloroquine: Modifying An Old Drug To Make It A Little Sweeter, Richard Sleightholm

Theses & Dissertations

Hydroxyethyl starch (HES) is a clinically used polysaccharide colloidal plasma volume expander. The goal of this study was to synthesize HES modified with hydroxychloroquine (HCQ) as a novel polymeric drug with the ability to inhibit the invasive character of pancreatic cancer (PC) cells. HES was conjugated with HCQ using a simple carbonyldiimidazole coupling to prepare Chloroquine-modified HES (CQ-HES). CQ-HES with various degrees of HCQ substitution were synthesized and characterized. In vitro studies showed CQ-HES to have a similar toxicity profile as HCQ. Confocal microscopy revealed the propensity of CQ-HES to localize to lysosomes, and mechanistic studies confirmed the ability of …


Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman 2019 University of Nebraska Medical Center

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …


Long-Acting Nanoformulated Small Molecule Inhibitor Prodrugs For Antiviral Treatment And Prevention, Nathan Smith 2019 University of Nebraska Medical Center

Long-Acting Nanoformulated Small Molecule Inhibitor Prodrugs For Antiviral Treatment And Prevention, Nathan Smith

Theses & Dissertations

Over 30 years of antiretroviral therapy (ART) has transformed human immunodeficiency virus type one (HIV-1) outcomes from certain death to a nearly complete and normal life. Though disease growth has slowed, the virus still creates substantial co-morbid diseases as well as social and economic burdens worldwide. Lack of success with curative efforts combined with shortcomings in global treatment remain to be properly addressed. The requirement for daily use of combination antiretroviral drugs (ARVs) in low to middle income countries - where the majority of the HIV-1 positive population resides - can lead to breaks in regimen adherence due to a …


Synthesis And Characterization Of American Ginseng Polysaccharides Nanoparticles, Vincent Lee 2019 The University of Western Ontario

Synthesis And Characterization Of American Ginseng Polysaccharides Nanoparticles, Vincent Lee

Electronic Thesis and Dissertation Repository

This project was concerned with the synthesis of nanoparticles (NPs) by microfluidics from bulk ginseng polysaccharides (PS) isolated from American ginseng to design a new delivery system to improve the bioavailability of PS. Physicochemical analyses showed products of nanosizing as unimodal spheres with a diameter of ~19 nm. Pharmacological characterization studies in vitro of these nanoparticles of PS (NPPS) have demonstrated heightened immunostimulatory activity, and enhanced penetration across skin cell monolayer, which could be considered as evidence of increased bioavailability. Studies using PS sub-fractions with different molecular weights for NPPS synthesis showed that molecular weights is one of the parameters …


Peptide Functionalized Surfactant Msns, Sonia Barrett 2019 Kansas State University Libraries

Peptide Functionalized Surfactant Msns, Sonia Barrett

Kansas State University Undergraduate Research Conference

Antibiotic resistance in bacteria has become a rising problem since the first antibiotic was created, further aggravated by the improper overuse to treat common infections, because of this pharmaceutical companies must keep making new and stronger antibiotics. Surfactants are plentiful and effective killers of many surface bacteria and are also varied in their structure, all have a hydrophilic head and long hydrophobic carbon chain. These long hydrophobic carbon chains can pierce through the lipid bilayers that make up bacteria cell membranes and cause cytoplasmic leakage and lysis of the cell wall, leading to cell death. One proposed surfactant is synthesized …


Therapeutic Peptide Sequences And Gatekeepers Loaded With Mesoporous Silica Nanoparticles, Dursitu Hassen 2019 Kansas State university

Therapeutic Peptide Sequences And Gatekeepers Loaded With Mesoporous Silica Nanoparticles, Dursitu Hassen

Kansas State University Undergraduate Research Conference

The research community is developing and looking into new ways of effectively delivering anti-cancer treatment. According to National Cancer Institute over 1.5 million new cases of cancer are predicted in the United States, just alone in 2018. The major hurdles that have been identified by scientists are finding mechanisms that assist in decreasing the side effects of cancer treatment and to increase the effectiveness of the drug. In our lab, a highly toxic peptide sequence, SA-K6L9-AS is encapsulated in MSNs (mesoporous silica nanoparticles) and capped with a gatekeeper. The function of a gatekeeper is preventing the …


Design Of Sensors For In-Vivo Detection Of Cancer Related Enzymes, laura soto 2019 Kansas State University Libraries

Design Of Sensors For In-Vivo Detection Of Cancer Related Enzymes, Laura Soto

Kansas State University Undergraduate Research Conference

Cancer continues to be among the leading causes of death worldwide. In 2018, there were approximately 9.6 million cancer deaths, just in the United States alone, there were 1.7 million new cancer cases and 600,000 deaths. That is why, there is an urgent need for better ways to battle cancer. Therefore, the goal of this project is to create a nanobiosensor which would have T1 and T2 based imaging capabilities to measure cancer enzymatic activity. The diagnostic tool would be useful to differentiate between benign and malignant tumors in-vivo and to quantify the effect of cancer treatments, such …


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