The redox... ]]> Nathaniel Wilkens Hodgson http://iris.lib.neu.edu/pharm_sci_diss/30 http://iris.lib.neu.edu/pharm_sci_diss/30 Tue, 02 Apr 2013 12:57:36 PDT The vaccine delivery systems containing adjuvants modulate magnitude, breadth, quality, and longevity of immune responses to antigen vaccinations aimed to induce cell-mediated immunity. For vaccines targeting tumor antigens, adjuvant-based delivery systems are necessary to overcome various tolerance mechanisms and facilitate induction of cytotoxic T lymphocytes (CTLs) that can traffic to and lyse malignant cells. The objective of this doctoral thesis project was to develop a multi-compartmental vaccine delivery system for safe and efficient delivery of a variety of melanoma antigens for immunotherapy.

Water-in-oil-in-water (W/O/W) multiple emulsions-based multi-compartmental vaccine delivery systems containing the gp100 peptide or hgp100 plasmid DNA was prepared... ]]> Mayurkumar Chimanlal Kalariya http://iris.lib.neu.edu/pharm_sci_diss/29 http://iris.lib.neu.edu/pharm_sci_diss/29 Tue, 02 Apr 2013 12:30:49 PDT The endocannabionoid signaling system is composed of two main cannabinoid receptors (CB1 and CB2 ), their principal endogenous ligands (anandamide (AEA) and 2-arachidonoylglycerol (2-AG)) and enzymes primarily responsible for degrading endocanabinoids such as fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MGL), abhydrolase domain-containing protein-6 and N-acylethanolamine-hydrolyzing acid amidase (NAAA) that are responsible for reduction of endocanabinoid system activity and its consequent (patho) physiological effects. Although FAAH may inactivate 2-AG in vitro, its main in vivo biological substrate is anandamide, whereas MGL exclusively hydrolyzes 2-AG to stoichiometric amounts of arachidonic acid (AA) and glycerol in vivo. Unlike anandamide, that is a... ]]> Ioannis L. Karageorgos http://iris.lib.neu.edu/pharm_sci_diss/28 http://iris.lib.neu.edu/pharm_sci_diss/28 Mon, 01 Apr 2013 09:36:06 PDT The pathogenesis of many diseases involves uncontrolled inflammation. Overactive inflammatory response to remove pathogens sometimes leads to undesirable outcome of collateral tissue damage. The adenosine-A2A adenosine receptor (A2AR) pathway plays an important role in protecting tissues from excessive damage during inflammation by suppressing immune responses including T cell activation. Local levels of extracellular adenosine are known to increase in tissues receiving insufficient oxygen supply (hypoxia). Tumors and local inflammation sites are hypoxic and contain high levels of extracellular adenosine. Therefore, in patho-physiological conditions such as infection and cancer, T cells may have to get activated in an adenosine rich environment.... ]]> Radhika G. Kini http://iris.lib.neu.edu/pharm_sci_diss/27 http://iris.lib.neu.edu/pharm_sci_diss/27 Mon, 01 Apr 2013 08:33:05 PDT Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels consisting of a combination of at least 17 possible subunits. Although most receptor subtypes are heteromeric, α7 subunits can assemble into homomeric receptors. α7 nicotinic receptors are the 2^nd most highly expressed nicotinic receptor in the brain, and their high permeability to calcium ions allows participation in calcium-dependent processes such as neurotransmitter release and immune modulation. Although these receptors have been well-studied, α7-mediated STAT3 signaling and α7 maturation remain unclear. The two major hypotheses we are investigating stem from these issues. The first hypothesis, regarding α7-mediated STAT3 activation, is that α7... ]]> Thomas Martin Koperniak http://iris.lib.neu.edu/pharm_sci_diss/26 http://iris.lib.neu.edu/pharm_sci_diss/26 Wed, 27 Mar 2013 09:48:26 PDT ECG and serum CK-MB (creatinine kinase) or cardiac troponin analyses are the routine tests for the diagnosis of myocardial necrosis. Borderline CK-MB elevations and uninterpretable ECGs are common emergency room encounters. Elevation of troponin levels do not occur until about 6 hours after the onset of chest pain. Additional complications occur in patients who are brought to the hospital days after the onset of chest pain. These in vitro laboratory tests can not distinguish between new and old infarcts besides they do not provide information on infarct size as is the case with non-Q wave myocardial infarction where infarct size... ]]> Rajiv Panwar http://iris.lib.neu.edu/pharm_sci_diss/25 http://iris.lib.neu.edu/pharm_sci_diss/25 Tue, 26 Mar 2013 08:03:46 PDT Cannabis has been used medicinally and recreationally for several centuries, commonly in the form of the plant's dried leaf/flower ("marijuana"). Δ⁹- Tetrahydrocannabinol (Δ⁹-THC) is the primary psychoactive component of cannabis and is prescribed as a pharmaceutical (Dronabinol^®) to stimulate appetite in AIDS patients, and to treat nausea and vomiting for patients undergoing chemotherapy. Δ⁹-THC is also under clinical investigation as an agonist-based therapy to combat cannabis dependence and addiction. Nabilone^® is a synthetic Δ⁹-THC analog sold as a prescription medication for treating emesis and as an analgesic for neuropathic pain. However, Dronabinol^® and Nabilone^® therapies suffer from several drawbacks, including... ]]> Rishi Sharma http://iris.lib.neu.edu/pharm_sci_diss/24 http://iris.lib.neu.edu/pharm_sci_diss/24 Tue, 19 Mar 2013 13:47:35 PDT Endogenous immune regulatory mechanisms exist to protect healthy tissue from collateral damage by overactive immune cells during inflammation. It has been found that extracellular adenosine can suppress pro-inflammatory activities through A2A adenosine receptors (A2ARs) on immune cells. This function of endogenous adenosine is non-redundant and has been regarded recently as a critical immune-regulatory negative feedback mechanism. Inflammatory responses in the liver have been shown to be under the control of A2AR-mediated anti-inflammatory pathway. The current study was designed to investigate the critical target of adenosine-mediated regulation of acute hepatitis. Experiments employing a murine model of acute hepatitis indicated exacerbated liver... ]]> Meenakshi Subramanian http://iris.lib.neu.edu/pharm_sci_diss/23 http://iris.lib.neu.edu/pharm_sci_diss/23 Tue, 19 Mar 2013 10:44:38 PDT The development of improved pharmacotherapeutics for treating cannabinoid dependence has presented many challenges. This report will discuss these challenges as well as use an animal model to study cannabinoid dependence by incorporating traditional methodologies (e.g., tetrad assay) and profiling novel cannabinoid ligands with distinct pharmacological properties/modes of action by evaluating their pharmacological effects on CB1-receptor related physiological and behavioral endpoints. Initial steps were made to characterize acutely AM2389, a CB1-receptor agonist, in the tetrad assay (i.e., locomotor activity, paw thermal stimulation, inverted screen test/catalepsy bar test and rectal temperature) as a novel approach for inducing dependence with greater potency and... ]]> Sherrica Tai http://iris.lib.neu.edu/pharm_sci_diss/22 http://iris.lib.neu.edu/pharm_sci_diss/22 Tue, 19 Mar 2013 09:46:06 PDT Fundamental progress in cancer biology has resulted in remarkable advances in cancer therapy. The goal now is to translate this knowledge in effective therapies. The major problem in cancer therapy is targeting the tumor site efficaciously and avoiding the undesired side effects at non-target sites. Nanocarriers like liposomes and micelles help to enhance delivery of therapeutics, influence the pharmacokinetic profile, drug metabolism and promote accumulation of the drug in the pathological area. The major long term goal of this project was to develop optimal delivery systems, capable of delivering small drug molecules like ascorbate and biotherapeutics like small interfering RNA... ]]> Onkar Shripad Vaze http://iris.lib.neu.edu/pharm_sci_diss/21 http://iris.lib.neu.edu/pharm_sci_diss/21 Mon, 26 Nov 2012 13:43:12 PST A tumor is an abnormally growing mass of cells. Ordinary chemotherapeutic agents used to prevent tumor growth produce more side effects and less than desired therapeutic effect. Targeted drug-delivery systems are necessary to provide and maintain an optimum drug concentration in target tissues and cells. Long-circulating nanoparticles have the ability to passively and actively target tumors and deliver the anticancer drugs. Passive targeting can be achieved by prolonged circulation and retention of the drug-loaded nanoparticles in the tumor, via enhanced permeability and retention (EPR) effect. Active targeting is possible by attaching various ligands to the nanoparticles to specifically target the... ]]> Anjali Vasant Apte http://iris.lib.neu.edu/pharm_sci_diss/20 http://iris.lib.neu.edu/pharm_sci_diss/20 Wed, 14 Nov 2012 09:01:43 PST Objective : Conventional chemotherapy is often accompanied by severe side-effects in cancer treatment owing to its inability to kill tumor cells specifically. The use of targeted pharmaceutical nanocarriers has improved the pharmacokinetic and pharmacodynamic properties of chemotherapy. Ongoing challenges for targeted delivery include the search for alternative ligands (e.g. "substitute antibodies") and development of methods for their conjugation with nanomedicines. The phage display technique is emerging as a powerful tool to identify tumor recognition molecules. The objective of the project is to integrate phage display technology with nanocarrier-based drug delivery systems (liposomes and micelles) for advanced targeted drug delivery. The... ]]> Tao Wang http://iris.lib.neu.edu/pharm_sci_diss/19 http://iris.lib.neu.edu/pharm_sci_diss/19 Thu, 25 Oct 2012 07:32:58 PDT Part I

Delta-9-tetrahydrocannabinol (THC) and (-)-cannabidiol (CBD) are the major constituents of Cannabis sativa (marijuana). (-)-CBD shares many of delta-9-THC's therapeutic properties without inducing negative psychotropic effects. These include potential medicinal uses for anti-inflammation, neuroprotection, anxiolytic, anti-nausea and anti-cancer that are all of great therapeutic importance. The clinical potential of (-)-CBD has been realized with the recent approval of Sativex® in Canada, a drug consisting of a 1:1 mixture of delta-9-THC and (-)-CBD for relief of neuropathic and cancer-related pain. Nonetheless, the levorotatory (-)-CBD natural product binds with low affinity to the two principal cannabinoid (CB) G protein-coupled receptors, CB1R... ]]> Marsha Rebecca D’Souza http://iris.lib.neu.edu/pharm_sci_diss/18 http://iris.lib.neu.edu/pharm_sci_diss/18 Fri, 29 Jun 2012 08:16:38 PDT Nanopreparations, such as micelles, liposomes and polymeric microcapsules are used to incorporate diagnostic and therapeutic agents in order to improve their performance. Lipid-core nanopreparations composed of polymeric micelles were employed to incorporate quantum dots for near infrared imaging of tumors. Tumors were imaged rapidly at half the dose of a commercially available quantum dot formulation. Additionally, these quantum dots containing polymeric micelles were targeted with a cancer-specific monoclonal antibody (2C5) that selectively accumulated in the tumor. This system produced a higher signal compared to untargeted quantum dot micelles.

Cancer was also detected indirectly by making use of circulating biomarkers, such... ]]> Jaydev Rajaram Upponi http://iris.lib.neu.edu/pharm_sci_diss/17 http://iris.lib.neu.edu/pharm_sci_diss/17 Thu, 28 Jun 2012 11:54:54 PDT Objective

The use of lipid-based pharmaceutical nanocarriers, such as lipid-core polymeric micelles and liposomes have improved the pharmacokinetic and pharmacodynamic properties of many pharmaceuticals, especially in chemotherapy. These delivery systems have not only helped in increasing the solubility of poorly soluble chemotherapeutic drugs but have also acted as reservoir of large molecular weight active pharmaceutical ingredients (API) like proteins. The objective of the thesis was to explore surface modification options to further enhance the delivery of pro-apoptotic small molecules for cell-specific delivery and proteins for intracellular delivery. The thesis has been divided into two sections.

Section a

The purpose of... ]]> Ritesh Vasudevan Thekkedath http://iris.lib.neu.edu/pharm_sci_diss/15 http://iris.lib.neu.edu/pharm_sci_diss/15 Fri, 15 Jun 2012 11:32:15 PDT The use of lipid-based pharmaceutical nanocarriers, such as lipid-core polymeric micelles and liposomes have improved the pharmacokinetic and pharmacodynamic properties of many pharmaceuticals, especially in chemotherapy. These delivery systems have not only helped in increasing the solubility of poorly soluble chemotherapeutic drugs but have also acted as reservoir of large molecular weight active pharmaceutical ingredients (API) like proteins. The objective of the thesis was to explore surface modification options to further enhance the delivery of pro-apoptotic small molecules for cell-specific delivery and proteins for intracellular delivery. The thesis has been divided into two sections.

Section a

The purpose of this... ]]> Ritesh Vasudevan Thekkedath http://iris.lib.neu.edu/pharm_sci_diss/14 http://iris.lib.neu.edu/pharm_sci_diss/14 Wed, 30 May 2012 07:56:51 PDT Current standard cancer therapies include surgery, chemotherapy and radiation therapy. Although surgery is generally effective in the treatment of primary cancerous lesions, surgical resection of malignant tumors may not result in complete cure. By the time a tumor is detected by the existing diagnostic methods, it can be assumed that metastases may already have occurred and spread. These metastatic sites are not identified at such early stages by existing methods such as X-ray, ultrasound, Computed Tomography (CT) scans or even Nuclear Magnetic Resonance Imaging (MRI) because of poor limit of detection. Small cancerous lesions are difficult to detect in vivo... ]]> Vishwesh A. Patil http://iris.lib.neu.edu/pharm_sci_diss/13 http://iris.lib.neu.edu/pharm_sci_diss/13 Thu, 09 Feb 2012 08:00:15 PST Targeting the tumor vascular supply in a homogenous manner is a difficult task to achieve with the use of pegylated cationic liposomes (PCLs) alone. Our formulation consisting of bevacizumab conjugated to the distal end of PEG on PCLs was thus developed in an effort to eliminate some of this heterogeneity as well as to increase tumor targeting overall. This study focuses on pancreatic cancer, which has the poorest five-year survival rate of all cancers because of its late diagnosis. The addition of bevacizumab will target tumor areas because it binds to VEGF which is secreted by tumors in high levels.... ]]> Geoffrey M. Kuesters Cancer - Treatment Liposomes Bevacizumab Pancreas - Cancer http://iris.lib.neu.edu/pharm_sci_diss/12 http://iris.lib.neu.edu/pharm_sci_diss/12 Wed, 08 Feb 2012 10:44:19 PST Macromolecular drugs have great promises for cancer treatment, such as the pro-apoptotic peptide D-(KLAKLAK)2 and the bcl-2 antisense oligodeoxynucleotide G3139. However, these macromolecules require efficient drug carriers, like liposomes, to deliver them inside cells. Also, if these macromolecules can be combined in a single liposome, the cancer cell killing will be greater than using just one. With this possibility in mind, cationic liposomes (CLs) were elaborated to encapsulate both macromolecules and deliver them inside cells. Later, surface modification of CLs was investigated through the addition of polyethylene glycol (PEG) to obtain long-circulating liposomes.

CLs were prepared through charge alternation among... ]]> Claudio Borges Falcao Cancer - Treatment Liposomes Macromolecules Drugs