Pharmacy and Pharmaceutical Sciences Commons^™

Antiviral Peptide Nanocomplexes As Potential Therapeutics For The Treatment Of Infectious Diseases, Jinjin Zhang

Theses & Dissertations

Hepatitis C Virus (HCV) is recognized as a major burden in global public health, which can be further exacerbated by several cofactors such as human immunodeficiency virus (HIV). Currently, there is no vaccine for HCV. The emergence of potent and highly specific direct-acting antivirals (DAA) has marked a new era in HCV therapy, however, the remaining issues like affordability, genotype dependency, and potential resistance still necessitate the development of additional therapeutic approaches to be used instead or in combination with DAA.

Recently, the antiviral peptide C5A (in our studies designated as p1) and its cationic derivative p41 have been identified …

Biodegradable Hybrid Nanogels For Combination Chemotherapy, Swapnil Desale

Theses & Dissertations

Combination chemotherapy is commonly used to treat cancer, because such a therapy regimens usually involve sequential administration of multiple drugs and allow targeting different cell signaling pathway. The co-delivery of drug combination at a controlled ratio via the same vehicle is offering the advantages such as spatial-temporal synchronization of drug exposure, synergistic therapeutic effects and suppression of drug resistance. Undoubtedly, there are several molecular and pharmacological factors that determine the effectiveness of drug combinations. A rationally designed drug combination is required since certain drug ratios and the definitive exposure to the targets of interest can only be synergistic while others …

Pamam Dendrimers As Promising Nanocarriers For Rnai Therapeutics, Prashant Kesharwani, Sanjeev Banerjee, Umesh Gupta, Mohd Cairul Iqbal Mohd Amin, Subhash Padhye, Fazlul H. Sarkar, Arun K. Iyer

Pharmaceutical Sciences Faculty Publications

Therapeutics based on RNA interference mechanisms are highly promising for the management of several diseases including multi-drug resistant cancers. However, effective delivery of siRNAs and oligonucleotides still remains challenging. In this regard, hyper-branched, PAMAM dendrimers having unique three-dimensional architecture and nanoscale size, with cationic surface charge can potentially serve as siRNA condensing agents as well as robust nano-vectors for targeted delivery. In addition, their surface functionality permits conjugation of drugs and genes or development of hybrid systems for combination therapy. Thus far, in vitro cellular testing of dendrimer-mediated siRNA delivery has revealed great potential, with reports on their in vivo …

Lipopolysaccharide Induced Map Kinase Activation In Raw 264.7 Cells Attenuated By Cerium Oxide Nanoparticles, Vellaisamy Selvaraj, Niraj Nepa, Steven Rogers, Nandini D.P.K. Manne, Ravi K. Arvapalli, Kevin M. Rice, Shinichi Asano, Erin Fankenhanel, J. Y. Ma, Tolou Shokuhfar, Mani Maheshwari, Eric R. Blough

Pharmaceutical Science and Research

High mortality rates are associated with the life threatening disease of sepsis. Improvements in septic patient survivability have failed to materialize with currently available treatments. This article represents data regarding a study published in biomaterials (Vellaisamy et al., Biomaterials, 2015, in press). with the purpose of evaluating whether severe sepsis mortality and associated hepatic dysfunction induced by lipopolysaccharide (LPS) can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the method and processing of raw data related to our study publish in Biomaterials and Data in Brief (Vellaisamy et al., …

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. …

Targeted Magnetite Tissue Delivery For Antiretroviral Pharmacokinetics, Tianyuzi Li

Theses & Dissertations

Pharmacokinetics and pharmacodynamics studies are required for bench to bedside translation of any new drug, formulation or device. Multifunctional magnetite nanocarriers enable magnetic resonance imaging tracking of nanomaterial encased antiretroviral drugs serving to improve the effectiveness of formulation developments. Targeting ligands used to deliver nanoparticles to HIV harboring cells can be tested using multifunctional magnetite nanocarriers. To this end, two types of magnetite nanocarriers were developed. These included small magnetite antiretroviral therapy particles. The second were ALN-PEG coated magnetite particles for testing macrophages targeting ligands. Overall, these works should serve to speed the development of long acting nanoformulated ART to …

New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number.

METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population.

RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with …

Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne Phd, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel

Pharmaceutical Science and Research

The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation …

Polymeric Nanoparticle-Based Delivery Of Microrna-199a-3p Inhibits Proliferation And Growth Of Osteosarcoma Cells, Linlin Zhang, Arun K. Iyer, Xiaoqian Yang, Eisuke Kobayashi, Yuqi Guo, Henry Mankin, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain …

Mdr1 Sirna Loaded Hyaluronic Acid-Based Cd44 Targeted Nanoparticle Systems Circumvent Paclitaxel Resistance In Ovarian Cancer, Xiaoqian Yang, Arun K. Iyer, Amit Singh, Edwin Choy, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of …