Medicine and Health Sciences Commons^™

Ligand-Installed Polymeric Nanocarriers For Combination Chemotherapy, Xinyuan Xi

Theses & Dissertations

Combination chemotherapy remains the mainstay of cancer treatment because such strategy targets different cell signaling pathways to decrease the likelihood of developing protective mechanisms by cancer cells, thereby delaying the onset of recurrence and prolonging the survival. The co-delivery of binary drug combination via a single nanocarrier provides benefits in reducing dose-limiting toxicities, improving the pharmacokinetic properties of the cargo, spatial-temporal synchronization of drug exposure, and synergistic therapeutic effects. Rational design of such regimen is crucial for maximizing the therapeutic effects since only certain drug ratios exposed to the target might be synergistic while other ratios exert additive or even …

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 …

Development Of Novel Therapies For The Treatment Of Inflammatory Bowel Disease, Shrey Kanvinde

Theses & Dissertations

Inflammatory bowel disease (IBD) is a chronic and remittent inflammation of the gastrointestinal tract (GIT). Despite extensive research efforts, there is no cure nor a well-defined pathogenesis for IBD. Loss of epithelial barrier function, increased colonic immune cell infiltration and upregulation of pro-inflammatory cytokines are the hallmarks of IBD. Despite treatments like painkillers, aminosalicylates, steroids, and biologics, almost 70% patients require surgery at least once in their life time. The main limitation with most of the current treatments is they are either absorbed systemically or administered systemically resulting in adverse side effects. As a result, there is a huge unmet …

Delivery Of Small Molecule And Rna For The Treatment Of Type 1 Diabetes And Prostate Cancer, Di Wen

Theses & Dissertations

The aim of this thesis is to develop combination therapy using a small molecule and RNA including siRNA, shRNA, or miRNA inhibitor for the treatment of type 1 diabetes and prostate cancer. New amphiphilic biodegradable polymers capable of co-delivering small hydrophobic molecules and RNAs or human bone marrow-derived mesenchymal stem cell (hBMSC) for co-delivery of an shRNA and a miRNA inhibitor were used as drug delivery platform. The drug delivery properties were evaluated in vitro and in vivo islet transplantation, subcutaneous and orthotopic prostate cancer models.

In Chapter 1, an overview of prostate cancer, the role of miRNA and …

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 …

Polymeric Nanocarriers For Treatment Of Melanoma And Genetically Modified Mesenchymal Stem Cells To Improve Outcome Of Islet Transplantation, Vaibhav Mundra

Theses & Dissertations

Melanoma is a lethal malignancy with limited treatment options for advanced metastatic stages. New targeted therapeutic options with discovery of BRAF and MEK inhibitors have shown significant survival benefit. Despite the recent progress, inefficient tumor accumulation and dose limiting systemic toxicity remains pressing challenges for treating metastatic melanoma and there is a need for drug delivery approach to improve therapeutic index of chemotherapeutics. Nanoparticle based drug delivery represents promising approach to enhance efficacy and reduce the dose limiting systemic toxicity. Nanoparticles can be formulated either by physical encapsulation of drugs or by covalent conjugation of drugs to the polymeric backbone. …