Life Sciences Commons^™

Development Of Chloroquine-Containing Hpma Copolymers For Drug Delivery, Fei Yu

Theses & Dissertations

Abstract

Development of Chloroquine-containing HPMA Copolymers for Drug Delivery

Fei Yu, Ph.D.

University of Nebraska Medical Center, 2018

Supervisor: David Oupický, Ph.D.

Synthetic polymers have been extensively explored for improved delivery of anticancer agents. Polymers can be designed as either carriers of existing drugs or as polymeric drugs with intrinsic pharmacological activity. Advantages of such polymeric drugs include common positive features of polymer-drug conjugates, such as targeted delivery of drugs, altered pharmacokinetic and biodistribution, improved drug safety, but also favorable pharmacological activities due to multivalent receptor-ligand interactions.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are safe drugs that have been in clinical …

The Opposing Roles Of Glun2c And Glun2d Nmda Receptor Subunits In Modulating Neuronal Oscillations, Zhihao Mao

Theses & Dissertations

N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels consisting of two GluN1 subunits and two other subunits from among GluN2A-2D and GluN3A-3B subunits. NMDARs play critical roles in synaptic plasticity, learning and memory, and higher brain function such as cognition and perception. Dysfunction of NMDARs (hyper-function and hypo-function of NMDARs) are related to various diseases, including stroke, schizophrenia, Alzheimer’s disease, and others. However, to date, NMDARs antagonists have mostly failed in clinical trials due to adverse effects.

NMDARs antagonists replicate the core symptoms of schizophrenia which may underlie its ability to alter neuronal oscillations in the neural circuitry of different brain …

Development Of Macromolecular Prodrug Conjugates For The Diagnosis And Treatment Of Musculoskeletal Diseases, Xin Wei

Theses & Dissertations

Macromolecular prodrug conjugate is a promising strategy for better diagnosis and treatment of musculoskeletal diseases. Our lab has pioneered this effort and has successfully developed multiple prodrug formulations. The general approach we have taken is to incorporate active ingredient (AI, including imaging probe or therapeutic agents) containing monomers into water-soluble and biocompatible polymers, such as N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymers. Structural parameters of these polymeric prodrugs, such as molecular weight (MW), drug loading, prodrug activation mechanism and the selection of drug payload may greatly affect therapeutic efficacy and the safety of the macromolecular prodrugs. To investigate the impact of these …

Investigation Of P-Glycoprotein (Pgp) Induction By Pgp Substrates To Induce Paclitaxel Resistance In Ovarian Cancer Cells, Ryker Penn

Theses & Dissertations

The purpose of this study was to investigate the development of chemotherapeutic resistance to paclitaxel in ovarian cancer cells after treatment with drugs that are substrates for P-glycoprotein (PGP). A core concept of this experiment was to identify if PGP substrate drugs could also act as PGP inducers after prolonged treatment in SKOV-3 ovarian cancer cells. In order to test this, SKOV-3 cells were exposed to either fexofenadine, a PGP substrate used as an antihistamine, or the chemotherapeutic drug vinblastine. After 42 days of drug treatment, ABCB1 gene expression was measured by qRT-PCR. Analysis of ABCB1 expression in treated cells …