Chemicals and Drugs Commons^™

The Development Of Polymeric Dexamethasone Prodrug Nanomedicines For The Treatment Of Lupus Nephritis, Zhifeng Zhao

Theses & Dissertations

Lupus nephritis (LN) is a significant cause of morbidity and mortality among lupus patients. Glucocorticoids (GCs) are uniformly used in clinical LN management. Their notorious toxicities, however, have hampered the long-term clinical application. To circumvent GCs’ adverse effects while maintaining their potent therapeutic efficacy, we have developed a micelle-forming polyethylene glycol (PEG)-conjugated dexamethasone prodrug (ZSJ-0228), which could passively target the inflamed kidney in NZB/W F1 lupus-prone mice. It was found that monthly ZSJ-0228 treatment for five months significantly reduced the incidence of nephritis in NZB/W F1 mice with an improved survival rate. Unlike the dose equivalent daily dexamethasone treatment, long-term …

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …

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 …

Development Of Hyaluronic Acid-Derived Macromolecular Agents For Multimodal Imaging Probes And Nanomedicine, William M. Payne

Theses & Dissertations

Cancer, one of the most challenging maladies facing modern medicine, is a complex family of diseases that requires a multifaceted treatment regime. In recent years, increased research effort has been placed on the development of nanoscale formulations as a potential method to improve therapeutic efficacy and offer better treatment. Both drug formulation and biomedical imaging has benefitted from the development of new, nanoscale agents. Hyaluronic Acid (HA), a naturally occurring glycosaminoglycan, is a promising platform for the development of new drug delivery systems. Furthermore, hyaluronic acid is the principal ligand for the cell surface receptor CD44, which is overexpressed on …

Near Infrared Gumbos And Nanogumbos For Biomedical Applications, Mi Chen

LSU Doctoral Dissertations

Recent advances in development of nanomaterials have provided great opportunities for cancer research. In this dissertation, nanoGUMBOS derived from a group of uniform materials based on organic salts (GUMBOS) were investigated for several biomedical applications including chemotherapy, photothermal therapy (PTT), and drug delivery. GUMBOS are solid-phase organic salts consisting of bulky cations and anions. Similar to ionic liquids, GUMBOS display highly tunable properties with counter-ions variation, but with a defined melting point range of 25–250 °C. Nanomaterials derived from GUMBOS, i.e. nanoGUMBOS, display enhanced properties at the nanoscale level. This dissertation focuses on development of near infrared IR780 nanoGUMBOS for …

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 …

One-Pot Syntheses And Characterizations Of “Click-Able” Polyester Polymers For Potential Biomedical Applications, James F. Beach Ii

Electronic Theses & Dissertations

In this study, a synthetic polyester polymer was designed using polyethylene glycol, sorbitol, glutaric acid and 4-pentynoic acid as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by Novozyme-435, an enzyme suitable for polyesterification of biocompatible compounds. The progress of the reaction was monitored with respect to time and vacuum exposure, with samples being subjected to standard characterization protocols. Polymers with high molecular weight and water solubility were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to cancer cells. This was achieved by employing a solvent diffusion method, wherein the polymer …

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo.

In vivo biodistribution and pharmacokinetics are affected by the physicochemical …

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 …