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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. …


Performance Study Of The Membrane Based Layered Double Hydroxides ‘Znal-Gh’ In The Purification Of Groundwater, Jaouad Zerhouni, Omar Qabaqous, Fouzia Rhazi Filali, Mohammed Naciri Bennani, Najib Tijani 2019 University of Moulay Ismail, Morocco

Performance Study Of The Membrane Based Layered Double Hydroxides ‘Znal-Gh’ In The Purification Of Groundwater, Jaouad Zerhouni, Omar Qabaqous, Fouzia Rhazi Filali, Mohammed Naciri Bennani, Najib Tijani

Karbala International Journal of Modern Science

The objective of this work is focused on the preparation and characterization of plan microfiltration membrane Zn3Al-Gh and the study of their efficiency in the treatment of ground water. This membrane was carried by using the support of the clay such as Ghassoul ‘Gh’ prepared by using dry uniaxial compaction method. The layered double hydroxides (LDH) based on Zn3Al-CO3with molar ratio (Zn2+/Al3+=3) was deposited on support by direct co-precipitation method.

The characterizations of the membrane LDH-Gh ‘Zn3Al-Gh’ and deposited layer Zn3Al-CO3, was done by scanning …


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

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and 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 …


Gemcitabine Combination Nano Therapies For Pancreatic Cancer, Kamalika Samanta, Saini Setua, Sonam Kumari, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan 2019 The University of Texas Rio Grande Valley

Gemcitabine Combination Nano Therapies For Pancreatic Cancer, Kamalika Samanta, Saini Setua, Sonam Kumari, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications and Presentations

Pancreatic cancer is one of the deadliest causes of cancer-related death in the United States, with a 5-year overall survival rate of 6 to 8%. These statistics suggest that immediate medical attention is needed. Gemcitabine (GEM) is the gold standard first-line single chemotherapy agent for pancreatic cancer but, after a few months, cells develop chemoresistance. Multiple clinical and experimental investigations have demonstrated that a combination or co-administration of other drugs as chemotherapies with GEM lead to superior therapeutic benefits. However, such combination therapies often induce severe systemic toxicities. Thus, developing strategies to deliver a combination of chemotherapeutic agents more securely …


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, …


Dextran-Coated Iron Oxide Nanoparticles As Biomimetic Catalysts For Biofilm Disruption And Caries Prevention, Yuan Liu 2019 University of Pennsylvania

Dextran-Coated Iron Oxide Nanoparticles As Biomimetic Catalysts For Biofilm Disruption And Caries Prevention, Yuan Liu

Dental Theses

Biofilms are surface-attached bacterial communities embedded within an extracellular matrix that create localized and protected microenvironments. Acidogenic oral biofilms can demineralize the enamel-apatite on teeth, causing dental caries (tooth decay). Current antimicrobials have low efficacy and do not target the protective matrix and acidic pH within the biofilm. Recently, catalytic nanoparticles were shown to disrupt biofilms but lacked a stabilizing coating required for clinical applications. Here, we report dextran-coated iron oxide nanoparticles termed nanozymes (Dex-NZM) that display strong catalytic (peroxidase-like) activity at acidic pH values, target biofilms with high specificity, and prevent severe caries without impacting surrounding oral tissues in …


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 …


Characteristics Of Nanoparticles Emitted From Kanthal A1 And Nichrome Heaters Used In Electronic Cigarettes, Kaushal Arvind Prasad 2019 Purdue University

Characteristics Of Nanoparticles Emitted From Kanthal A1 And Nichrome Heaters Used In Electronic Cigarettes, Kaushal Arvind Prasad

The Journal of Purdue Undergraduate Research

No abstract provided.


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 …


Nanoporous Gold And Other Related Materials, Keith Stine 2019 University of Missouri, St. Louis

Nanoporous Gold And Other Related Materials, Keith Stine

Chemistry & Biochemistry Faculty Works

No abstract provided.


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 …


Behavioral Responses To Gold Nanoparticle Exposure And H2o2-Induced Oxidative Stress In Caenorhabditis Elegans, Rachel Pride, Ashley Wagner 2019 Depaul University

Behavioral Responses To Gold Nanoparticle Exposure And H2o2-Induced Oxidative Stress In Caenorhabditis Elegans, Rachel Pride, Ashley Wagner

DePaul Discoveries

Gold nanoparticles (AuNPs) have been utilized in many biomedical disciplines, most notably cancer therapy and drug delivery. Recent research suggests that with specific peptide manipulation, AuNPs can deliver drugs across the blood-brain barrier (BBB), allowing for treatment of neurodegeneration and other neurological afflictions. Neurodegeneration has been shown to be caused by oxidative stress. The present experiment aimed to assess the effects of AuNPs on C. elegans behavior that had undergone H2O2-induced oxidative stress. It was predicted that worms exposed to both H2O2 and AuNPs would have higher survival, mechanosensation, and thrashing rates than …


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 …


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 …


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 …


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 …


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