Physical Sciences and Mathematics Commons^™

Development Of Biomolecule Nanoparticle Conjugate For Targeted Delivery Of Therapeutics, Peidong Wu

Doctoral Dissertations

Delivery of therapeutics specifically to the disease site is the final goal for the field of drug discovery. Considerable efforts in understanding disease biology have contributed to identifying novel therapeutics such as small molecules, proteolysis targeting chimeras (PROTACs), peptides, proteins, and nucleic acids. However, improving their efficacy as well as minimizing their off-target toxicity remains challenging. Developing vectors that could not only efficiently encapsulate these therapeutics but also direct these therapeutics to the target site is a potential solution to address these challenges. In this dissertation, a block-copolymer-based nanoparticle platform has been developed optimized, and decorated with various kinds of …

Synthesis And Biomedical Applications Of Hollow Iron Oxide Nanoparticles, Aloka S. Paragoda Arachchilage

Dissertations, Theses, and Capstone Projects

Nano-scale materials have gained much attention during the past few decades due to the stark differences in their properties compared to bulk material. Thus, they are being studied for a myriad of applications ranging from harnessing solar energy to diagnostics. This thesis focuses on the synthesis of hollow iron oxide nanoparticles using Galvanic replacement reactions and their application in drug delivery. Moreover, the use of a peptide precursor for the enhancement of exosomes is also discussed.

Chapter 1 discusses a simple and economical Galvanic approach used for the synthesis of hollow one-dimensional iron oxide nanotubes. In the initial reaction, the …

Developing Mesoporous Silica Nanoparticle-Based Stimuli-Responsive Nanocarriers For Delivery Of Small Molecule Therapeutics Against Colon Cancer Cells, Nisitha Lakmal Wellala Wijewantha

Dissertations and Theses

This dissertation delves into the innovative application of mesoporous silica nanoparticles (MSNs) for targeted drug delivery in colorectal cancer (CRC), one of the most prevalent and deadly forms of cancer worldwide. The initial focus of the research is on developing enzyme-responsive MSNs loaded with veratridine (VTD), an alkaloid derived from natural sources that demonstrates potent anticancer activity. The nanoparticles have been engineered to deliver VTD selectively to CRC cells, releasing the payload upon being exposed to specific enzymes primarily secreted by these cells. This strategy has dual advantages of amplifying the anticancer effects while minimizing potential side effects on healthy …

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 …

Development Of Stimuli-Responsive Liposomes For Drug Delivery Applications, Jinchao Lou

Doctoral Dissertations

Liposomes are spherical nano-assemblies that are proven to be effective drug delivery vehicles. Due to their unique bilayer structures, they are able to encapsulate both hydrophilic and hydrophobic drugs in their aqueous inner core and membrane bilayers, respectively. While liposomal delivery platforms exbibit numerous advantages, the therapeutic efficacy of these platforms would be enhanced by developing triggered release strategies such that one can tune the timing and location of the cargo release in a controlled manner. In this dissertation, we mainly present the development of stimuli-responsive liposomes targeting different disease-associated metabolites utilizing rationally designed synthetic lipid switches.

In Chapter 2, …

Investigating Ionic Current Rectification As A Means Of Controllable Drug Delivery Using Silica Nanoparticles And Nano Porous Membranes, Katie L. Nolan

Honors College Theses

This project investigates a novel ionic current rectification (ICR) phenomenon created by the opening and closing of nanopores by charged silica nanoparticles (SNPs) under electrophoretic flow. This voltage-controlled opening and closing of the pores can be exploited to allow delivery of nicotine through the pores at programmable intervals. The ICR phenomenon was thoroughly investigated by varying pH, buffer concentration, SNP concentration, and applied voltage range. The mechanism was also verified by testing with a 2-, 3-, and 5-electrode system. Potential cake layer formation was demonstrated in a longer ICR test, and the implications of this on the drug delivery mechanism …

The Development Of Novel Carbohydrate-Based Gelators And Their Applications As Advanced Soft Materials, Joedian Morris

Chemistry & Biochemistry Theses & Dissertations

Low molecular weight gelators (LMWGs) are attractive molecules that have been explored extensively due to their practical applications in many disciplines. These small molecules self-assemble forming solid-like gels via three-dimensional cross-linked networks with the solvent as the key component within the matrix. Carbohydrate-based LMWGs are small molecules that can form solid-like gels in water, organic solvents, and aqueous solutions. They have great potential to be utilized in different applications because carbohydrates are biocompatible and can be made from easily accessible and renewable resources. Designing gelators is still a challenge within the field, even though researchers have developed tools to predict …

Enhancing The Intracellular Availability Of Protein Cargoes In Polymer-Mediated Delivery, Christopher R. Hango

Doctoral Dissertations

Protein drugs, including antibodies, are rapidly emerging as the top-selling pharmaceuticals worldwide owing to their unparalleled specificity and biocompatibility. However, none of the currently-approved protein therapeutics act intracellularly, despite the vast majority of potential drug targets residing within the cell. This is due mainly to the paramount challenge of transporting hydrophilic macromolecular cargoes across the plasma membrane. As such, effective protein carriers are essential for the advancement of modern medicine. Despite significant advances, many challenges still plague protein delivery. Following membrane transduction, delivery vectors must preserve the structure and activity of their cargoes while transporting them to the correct subcellular …

End Group Modification Of Linear Dendritic Block Copolymers (Ldbcs), Chinwe Udemgba

Honors Theses

Linear dendritic block copolymers are amphiphilic molecules that consist of a dendritic hydrophilic portion and a linear hydrophobic portion. Its unique ability to self-assemble into spherical nanoaggregates while having the potential to uptake and transport both hydrophilic and hydrophobic drugs makes these polymers an item of interest in regard to the drug delivery field. The synthesis of polyamidoamine-polylactide linear dendritic block copolymers was designed to address the common issues in drug delivery systems, including problems in permeability, solubility, stability, specificity, and retention. Though this linear dendritic block copolymer has previously been synthesized in our lab with cationic amine surface functionalities, …

Development Of Biomaterials For Drug Delivery, Raquel De Castro

Graduate Theses and Dissertations

Drug delivery systems (DDS) have highly evolved in the last decades with the development of hydrogels and nanoparticles. However, high systemic uptake, side effects, low bioavailability, and encapsulation efficiency continue to be a major hurdle faced by such DDSs.

Nanoparticles and hydrogels can be specifically designed for targeted DDSs to mitigate some of the problems. This dissertation aimed to design two DDSs for ocular drug delivery and one for cancer treatment. The first project sought to develop chitosan nanoparticles (Cs-NP) using PEGDA as a copolymer to encapsulate gentamicin (GtS) for ocular drug delivery. Cs-NPs contain positive charges that can interact …

Elucidating The Interfacial Interactions Between Biomacromolecules And Functionalized Pamam-Based Materials For Biomedical Applications, Briana L. Simms

Electronic Theses and Dissertations

Polyamidoamine (PAMAM) is a dendrimer structure with a polypeptide backbone architecture. It has been utilized in a wide variety of applications but has found significant utility in biomedical applications. PAMAM has been studied extensively due to its globular structure that is similar to proteins found in the body. The branched architecture and overall size provide a favorable environment for host-guest interactions and allows for the loading of small molecules for therapeutic delivery. Although PAMAM has many benefits for use in the area of therapeutic delivery, a primary area of concern for this molecular architecture is the terminal amines that serve …

Antibacterial Coatings Derived From Novel Chemically Responsive Vesicles, Emily B. Mobley

Master's Theses

In order for a drug, or any material used for the purpose of eliciting a change in an organisms’ physical or chemical state, to be effective it must reach the intended target intact and for a sustained rate over time. Drug delivery systems encapsulate a drug to protect it from degradation, prevent side reactions, increase solubility, improve accumulation rates at target sites, and release drugs at a controlled rate. Controlled and sustained release of drugs is achieved by degradation of the carrier triggered by breaking dynamic chemical bonds caused by changes in the chemical environment such as pH or redox …

The Incorporation Of Phosphorus Into Polymer Networks For Drug Encapsulation And Release, Tristan D. Harrison

Electronic Thesis and Dissertation Repository

This thesis focuses on the incorporation of phosphonium salts into polymer networks for uses in drug delivery and antibacterial coatings. Compared to their ammonium analogues, which have been extensively investigated, phosphonium salts were of interest due to their different chemical properties and their higher chemical and thermal stabilities. The thesis describes the development of covalently crosslinked hydrogels, ionically crosslinked hydrogels and thin film materials to be utilized in the aforementioned applications.

Covalently crosslinked hydrogels were developed with the targeted application of drug delivery. The hydrogels were created by curing formulations with ultra-violet light. Then, anionic drug molecules were loaded, which …

Development Of Dual Functional Dna/Rna Nanostructures For Drug Delivery, Vibhav Amit Valsangkar

Legacy Theses & Dissertations (2009 - 2024)

In addition to the traditional biochemical functions, DNA and RNA have been increasingly studied as building blocks for the formation of various 2D and 3D nanostructures. DNA has emerged as a versatile building block for programmable self-assembly. DNA-based nanostructures have been widely applied in biosensing, bioimaging, drug delivery, molecular computation and macromolecular scaffolding. A variety of strategies have been developed to functionalize these nanostructures. The major advantage is that DNA is a very stable molecule and its base-pairing properties can be easily utilized to control and program the formation of desired nanostructures. In addition, some of these DNA/RNA nanostructures have …

Development Of Novel Tumor-Targeted Compounds For Boron Neutron Capture Therapy, Micah John Luderer

Arts & Sciences Electronic Theses and Dissertations

Glioblastoma multiforme (GBM) represents the most common primary brain tumor among adults. Despite surgical resection and aggressive chemoradiotherapy regimens, the current 2- and 5-year survival rates are only 27% and 9.8%, respectively. The low survival stems from the poor response to conventional therapy and underscores the critical need to develop new therapeutic approaches for GBM treatment. The high recurrence rate observed in GBM is in part attributed to the hypoxic (poorly oxygenated) tumor microenvironment. Hypoxic tumor conditions have been shown to increase metastasis, promote angiogenesis, and confer resistance to chemotherapy and radiation.

Hypoxic tissues are inherently radiation resistant due to …

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 …

Biocompatible, Responsive Polysoaps Via Raft Copolymerization For The Delivery Of Model Cancer Therapeutics, Mason Dearborn

Honors Theses

Many chemotherapeutic drugs are small, hydrophobic molecules that require water-soluble, biocompatible nanocarriers for enhanced vascular circulation. Existing polymeric carriers either conjugate the drug along a copolymer backbone or sequester drugs within a protected interior domain to be delivered to specific sites in the body. Such therapeutic systems must overcome a myriad of hurdles, beginning with complex, multi-step syntheses, followed by other inherent barriers that limit the efficiency of drug delivery at the targeted site. This work aims to circumvent a number of these issues using biocompatible, stimuli-responsive polysoaps that are capable of unimeric micelle formation, hydrophobic drug delivery, and triggered …

Design And Synthesis Of Stimuli-Responsive Polymeric Nanogels Towards Therapeutic Translation, Mallory R. Gordon

Doctoral Dissertations

In the application of delivery of therapeutics, nanostructures of various composition have been employed due to their capacity to act as a host for lipophilic payloads. Advances in the synthetic preparation, size, morphology, and chemical or physical characteristics of polymers have impacted their development and versatility. A detailed understanding of polymeric nanoparticle host-guest properties is crucial to their practical translation to specific delivery applications. Further, these features must be highly tailorable to overcome biological barriers, stably encapsulate their therapeutic contexts, and exhibit payload release selectively in the target environment. In this dissertation, we aim to rationally design polymeric nano-scale assemblies …

Biomedical Applications Of Hydrogels And Gumbos, Kelsey Elizabeth Mcneel

LSU Doctoral Dissertations

Sodium deoxycholate (NaDC) is a small bile salt that was used in this dissertation to produce gelation of tris(hydroxymethyl)amino-methane (TRIS) solutions above, below, and near the pKa of NaDC. These solutions respectively yielded a neutral gelator, a charged gelator, and a mixture of each. Impacts of ionic interactions on gel formation were studied in detail and showed that pH can be used to modify many hydrogel properties including sol-gel temperature, crystallinity, and mechanical strength. It was also observed that pH modification of the hydrogels affected nanoparticle formation. Nanoparticles derived from a Group of Uniform Materials Based on Organic Salts (nanoGUMBOS), …

Applications Of Cell-Derived Vesicles: From Single Molecule Studies To Drug Delivery, Faruk H. Moonschi

Theses and Dissertations--Chemistry

Single molecule studies can provide information of biological molecules which otherwise is lost in ensemble studies. A wide variety of fluorescence-based techniques are utilized for single molecule studies. While these tools have been widely applied for imaging soluble proteins, single molecule studies of transmembrane proteins are much more complicated. A primary reason for this is that, unlike membrane proteins, soluble proteins can be easily isolated from the cellular environment. One approach to isolate membrane proteins into single molecule level involves a very low label expression of the protein in cells. However, cells generate background fluorescence leading to a very low …

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 …

Nanoparticle As Supramolecular Platform For Delivery And Bioorthogonal Catalysis, Gulen Yesilbag Tonga

Doctoral Dissertations

Nanoparticles (NPs) are being investigated widely for many applications including imaging, drug delivery, therapeutics, materials, and catalysis due to their unique and tunable physical and chemical properties. Among NPs, gold nanoparticles (AuNPs) have attracted great attention due to ease of synthesis and surface functionalization, inertness of the core, biocompatibility, and functional versatility. Introducing supramolecular chemistry into the nanoparticle-based platforms brings out controllable properties, dynamic self assembly processes, and adjustable performance. My research has focused on the synthesis of AuNPs bearing different surface functionalities and their host-guest interactions with synthetic small molecules or commercially available hydrophobic catalysts for delivery and therapeutic …

Stimuli Responsive Polymeric Nanogels For Hydrophobics & Hydrophilics Delivery, Kishore Raghupathi

Doctoral Dissertations

Stimuli responsive nanoparticles have gained significant interest in the drug delivery research. The essential goal of drug delivery is to improve the efficacy of drugs by increasing their stability and bioavailability. Small molecule hydrophobic drugs face limited bioavailability due to their poor water solubility. Biologic drugs on the other hand, lack bioavailability because of their degradation by various enzymes encountered during blood circulation. For a systemic delivery approach, depending on site of drug action, delivery vehicles must pass through several contrasting micro environments before delivering the cargo selectively at the target site. Therefore, it is essential that a delivery vehicle …

Photopolymerization Synthesis Of Magnetic Nanoparticle Embedded Nanogels For Targeted Biotherapeutic Delivery, Daniel Jonwal Denmark

USF Tampa Graduate Theses and Dissertations

Conventional therapeutic techniques treat the patient by delivering a biotherapeutic to the entire body rather than the target tissue. In the case of chemotherapy, the biotherapeutic is a drug that kills healthy and diseased cells indiscriminately which can lead to undesirable side effects. With targeted delivery, biotherapeutics can be delivered directly to the diseased tissue significantly reducing exposure to otherwise healthy tissue. Typical composite delivery devices are minimally composed of a stimuli responsive polymer, such as poly(N-isopropylacrylamide), allowing for triggered release when heated beyond approximately 32 °C, and magnetic nanoparticles which enable targeting as well as provide a mechanism for …

Liposome-Coated Magnesium Phosphate Nanoparticle For Delivery Of Cytochrome C Into Lung Cancer Cells A549, Weizhou Yue

University of the Pacific Theses and Dissertations

Proteins are large biomolecules that have great therapeutic potential in treating many human diseases. However, chemical/enzymatic degradation, denaturation, and poor penetration into cells are some of the challenges for clinical use of intracellular proteins.

Previously, our group has developed cationic lipid-coated magnesium phosphate nanoparticle (LP MgP NP-CAT) formulations to enhance the intracellular delivery of the negatively charged protein catalase. The goal of the current research is to develop a formulation to deliver cytochrome c (CytC), a positively charged protein into lung cancer cells A549. Specifically, this thesis research prepares and tests liposome-coated magnesium phosphate nanoparticle for delivery of cytochrome c …

Synthesis And Performance Of Novel Supramolecular Tools For Single-Particle Cryogenic Electron Microscopy And Drug And Gene Delivery, Kyle J. Wright

Open Access Dissertations

High-resolution biomacromolecular structure elucidation is fundamentally important to structure-based drug design and basic research into complex biochemical processes. Cryo-EM is an emerging alternative to XRD and NMR that is complementary in many ways relative to XRD and NMR. Materials approaches to cryo-EM are anticipated to greatly facilitate the cryo-EM process, allowing progress toward a more high-throughput application of cryo-EM to address challenges in structural biology. ^ Various affinity-based approaches inspired by approaches previously introduced for 2D crystallization were developed for facilitation of cryo-EM. A library of affinity lipopolymer constructs were synthesized consisting of lipopolymers of various PEG molecular weights conjugated …

Engineering The Nano-Bio Interface Of Gold Nanoparticles For Biomedical Applications, Ying Jiang

Doctoral Dissertations

Gold nanoparticles (AuNPs) have emerged as a promising platform for a myriad of biomedical applications, including sensing, drug delivery, and antibiotics. In this thesis, I have studied and engineered the interface of AuNPs with different biological systems, demonstrating a large variety of biomedical applications by modulation of these interfaces. My research was initially focused on systematically tuning the physicochemical properties of nanoparticles to understand nano-bio interactions at the cellular level. The results demonstrate that size and surface charge of AuNP interact in an interrelated fashion to modulate nanoparticle internalization by cells, providing an engineering strategy for designing nanomaterials for drug …

Photodynamic Killing Of Human Cancer Cells With Smart Photosensitizer Materials And An Endoscopic Implement For Singlet Oxygen Delivery, Mihaela N. Minnis

Dissertations, Theses, and Capstone Projects

The thesis describes progress on probe tips for a microoptic device for the precise delivery of the components necessary for photodynamic therapy (PDT) in a highly localized and controllable fashion. The thesis also summarizes results of a photosensitized oxidation study. The work focused on i) developing a photoactive fluoropolymer surface that will release sensitizer drug molecule for use in PDT, ii) designing new probe tips surfaces for use as sensitizer support for a microoptic PDT device, iii) exploring strategies for covalent attachment of sensitizers and model compounds to Teflon/PVA surfaces with the aim of being coupled with our microoptic device, …

Addressing The Issues Of Drug Delivery Via Advanced Macromolecular Design, Brooks Allen Abel

Dissertations

The work described in this dissertation focuses on the development of synthetic approaches toward novel polymer architectures that specifically address the issues of in vivo drug delivery. Successful implementation of the synthetic methodologies described herein required fundamental investigations into the underlying chemistries in ways that now provide greater insights into the nature of the these chemical reactions.

In Section I, the synthesis of tunable pH- and CO₂-responsive sulfonamide-containing polymers using reversible addition-fragmentation chain transfer (RAFT) polymerization is described. Initially, poor polymerization control of methacryloyl sulfonamide (MSA) monomers was observed using traditional RAFT polymerization conditions. Ultimately, reducing the polymerization …

Responsive Supramolecular Assemblies Based On Amphiphilic Polymers And Hybrid Materials, Longyu Li

Doctoral Dissertations

The design and synthesis of responsive supramolecular assemblies are of great interest due to their applications in a variety of areas such as drug delivery and sensing. We have developed a facile method to prepare self-crosslinking disulfide-based nanogels derived from an amphiphilic random copolymer containing a hydrophilic oligo-(ethylene glycol)-based side-chain functionality and a hydrophobic pyridyl disulfide functional group. This thesis first provides a concept of studying the influence of Hofmeister ions on the size and guest encapsulation stability of a polymeric nanogel. The size and core density of nanogel can be fine-tuned through the addition of both chaotropes and kosmotropes …