Chemicals and Drugs Commons^™

Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana

Theses and Dissertations--Pharmacy

Cancer remains a real and present threat to global health. In the United States, according to cancer statistics, almost 40% of people will be diagnosed with cancer at some point in their lifetime. Conventional chemotherapy has become the mainstay for cancer treatment option. However, chemotherapeutic agents are plagued with problems such as poor aqueous solubility, chemical degradation, Bio instability, and off-site toxicity due to non-specificity. New drug modalities are needed to tackle the ever-growing burden on cancer. In recent times, the promise of nanotechnology has aided to develop drug delivery vehicles to facilitate the administration of potent chemotherapeutics. Nanoformulations such …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Influence Of Paclitaxel Nanomedicine On The Pancreatic Tumor Immune Components, Godwin Peasah-Darkwah

Theses and Dissertations

Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortalities in the U.S due to ineffective therapeutic options. Pancreatic tumors are highly desmoplastic and inhibit efficient uptake of therapeutic payloads. Paclitaxel (PTX) has been tested in PanCa therapy with marginally better clinical outcomes, but remain limited by its poor hemocompatibility, biodistribution and intracellular accumulation in tumor cells. Thus, we synthesized a next generation nanoparticle system for PTX to improve its pharmacokinetics and pharmacodynamics (PKPD) in treating PanCa. We also examined ability of the nano formulation to potentiate gemcitabine (GEM) activity in combating chemoresistance in the pancreatic tumor microenvironment …

The Use Of Silica Nanoparticles For Controlled Drug Delivery Of Nicotine, Jennifer C. Iwenofu

Honors College Theses

Drug molecules can be administered in different ways to the human body. Nanotechnology stands out over other alternatives by delivering drugs to specific locations and reducing reactivity time. In this research, the hydrogen bond between silica nanoparticles and the drug molecule, nicotine, were studied to controllably deliver nicotine by varying pH values.

System For Hiv-1 Treatment To The Brain, Caroline Rose Garcia

Theses and Dissertations

While HIV-1 treatment has been revolutionized by combination antiretroviral therapy in the past two decades, HIV-1 remains persistent in organs that don’t allow easy penetration of anti-HIV drugs (e.g., brain) and cause persistent HIV-1 infections and inflammation. Researchers have turned towards nanotechnology-based drug carriers to combat this challenge, such as nanodiscoidal bicelles (ND) and liposomes. Bicelles entrap the drug in their interior hydrophobic core until metabolized by the body, and the payload can be released at the desired location in a controlled, long-lasting dosage. This study investigated the toxicity and extended-release of an anti-HIV drug-loaded within ND and liposomes for …

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 …

Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin

Nanoscience and Microsystems ETDs

Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The …

Development Of In Situ Forming Hydrogels For Intra-Articular Drug Delivery, Andy Prince

Electronic Thesis and Dissertation Repository

Hydrogels are 3-dimensional crosslinked polymer networks that can absorb significant amounts of water. The physical properties associated with hydrogels affords them resemblance to biological tissues making them good candidates for biomedical applications. Many pharmaceuticals, specifically non-steroidal anti-inflammatory drugs (NSAIDs), have poor aqueous solubility, which limits their bioavailability and efficacy. People suffering from chronic osteoarthritis (OA) are required to frequently take large doses to mitigate pain, which can lead to serious side effects. Hydrogels are good strategies to deliver NSAIDs via articular injection because they can form solid gels in situ. This thesis describes the synthesis, formulation, mechanical testing, in …

Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel

Theses and Dissertations--Pharmacy

Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.

The goals of …

Development Of Polymeric Carriers For The Treatment Of Acute Kidney Injury, Yi Chen

Theses & Dissertations

Acute kidney injury (AKI) is a major kidney disease associated with high mortality and morbidity. Long-term AKI may lead to chronic kidney disease and end-stage renal disease. Several clinical trials failed due to lack of efficacy and undesired side effects. Studies showed that macromolecular delivery systems would be a promising method to target kidney, however, little is known about how physicochemical properties affects the polymers deposition in ischemia-reperfusion (I/R) AKI.

Gene therapy has been well studied as a promising therapeutic agent for several diseases, including cancer and AKI. Although small interfering RNA (siRNA) has been commonly used to treat AKI …

Fabrication And Modification Of Titania Nanotube Arrays For Harvesting Solar Energy And Drug Delivery Applications, Ahmed El Ruby Abdel Rahman Mohamed

Electronic Thesis and Dissertation Repository

The fast diminishing of fossil fuels in the near future, as well as the global warming caused by increasing greenhouse gases have motivated the urgent quest to develop advanced materials as cost-effective photoanodes for solar light harvesting and many other photocatalytic applications. Recently, titania nanotube arrays (TNTAs) fabricated by anodization process has attracted great interest due to their excellent properties such as: high surface area, vertically oriented, highly organized, one-dimensional, nanotubular structure, photoactivity, chemical stability and biocompatibility. This unique combination of excellent properties makes TNTAs an excellent photoanode for solar light harvesting. However, the relatively wide band gap energy of …

Magnetic Field-Induced Intramolecular Cyclization As A Trigger For Nanoparticle-Based Delivery Systems., Sara Katherine Biladeau

Electronic Theses and Dissertations

Magnetic nanoparticles (MNPs) are used in a variety of applications, including as agents for magnetic resonance imaging, generation of local hyperthermia, and as platforms for drug delivery. Iron-based MNPs are often coated with a shell, such as silica or gold, to increase biocompatibility for drug delivery applications. Many MNPs used for cancer therapy rely on either an internal trigger, such as a difference in pH, or an external trigger, such as light or an alternating magnetic field (AMF), to cause release of a payload, typically a chemotherapeutic drug. Internal triggers are appealing because drug release can be targeted to a …

Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh

Theses & Dissertations

Over the past decade, work from our laboratory has demonstrated the potential of targeted nanoformulated antiretroviral therapy (nanoART) to produce sustained high plasma and tissue drug concentrations for weeks following a single intramuscular (IM) administration that can suppress ongoing viral replication and mitigate dose associated viral resistance. While progress has occurred towards developing long-acting nanoformulations for protease and nonnucleoside reverse transcriptase (RT) inhibitors, development of nanoformulations of hydrophilic nucleoside RT inhibitor drugs have remained elusive. Abacavir (ABC); a hydrophilic molecule exhibited limited utilities to develop into long-acting nanoformulation platform. Furthermore, inefficient conversion of ABC to its biological active metabolites; carbovir …

Poly(Ester Amide) And Poly(Ethyl Glyoxylate) Nanoparticles For Controlled Drug Release, Amira Mohamed Moustafa

Electronic Thesis and Dissertation Repository

The objective of this research was to develop polymeric nanoparticles (NPs) having improved drug release properties for drug delivery. Poly(ester amide)s (PEAs) are promising biodegradable polymers. PEA NPs were prepared via emulsification-evaporation and salting-out methods and optimized through by varying different processing parameters. Polymer-model drug conjugates based on PEAs containing L-aspartic acid and rhodamine B were synthesized and used for NP preparation. Release behavior was studied and compared to a control system with physically encapsulated rhodamine B. It was shown that the release of rhodamine B from the covalent system did not show the burst effect and exhibited a slower …

Tuning Responsiveness Of Polypeptide Based Block Copolymers For Drug Delivery, Ashley J. Johnson

Dissertations

The goal of this dissertation was to tune the pH response and self-assembled morphologies of amphiphilic polypeptide block copolymers for use as drug delivery vehicles. Poly(L-lysine) and poly(L-glutamtic acid) are responsive, ionizable polypeptides that undergo secondary structure transitions, from α-helix to random coil, whereby the change in conformation of the peptide chain results in changes to the global morphology of a self-assembled system. The main focus of this work was to understand how changes in the polymer composition and the local environment can lead to control over the behavior of the overall system. First, the responsive behavior of poly(L-lysine) block …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Anti-Gd2 Etoposide-Loaded Immunoliposomes For The Treatment Of Gd2 Positive Tumors, Brandon S. Brown

Dissertations & Theses (Open Access)

Systemic chemotherapeutics remain the standard of care for most malignancies even though they frequently suffer from narrow therapeutic index, poor serum solubility, and off-target effects. Monoclonal antibodies that specifically bind antigens overexpressed on many tumors such as the ganglioside, GD2, can be conjugated to drug-loaded liposomes to create a targeted drug delivery system. In this study, we have encapsulated etoposide, a topoisomerase inhibitor effective against a wide range of cancers, in surface modified liposomes decorated with anti-GD2 antibodies. We characterized the properties of the liposomes using a variety of methods including dynamic light scattering, electron microscopy, and Fourier transformed infrared …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Synthesis And Analytical Evaluation Of Folate Conjugates For Use In Cancer Cell Detection, Sneha Reddy Kuthuru

All Capstone Projects

Recent clinical studies have shown the importance of folate receptor in drug delivery system as they increase the potency and reduce toxicity of many cancer therapies. The folate receptor alpha ( FR-a) binds with high affinity for folic acid and serves for receptor mediated transport of folate into cells. Folate is necessary for DNA metabolism and thus it is speculated that rapidly dividing cancer cells have an increased requirement for folic acid. It is known that FR-a levels are elevated in specific malignant diseases (solid tumors, leukemia) and thus the FR receptor serves as useful targeting moiety for the diagnosis …