Methionine synthase is a multi-domain enzyme and its linker domain termed `cap' is responsible for protecting cobalamin from dissociation and oxidation. In human brain, the cap domain of methionine synthase can be alternatively spliced in response to oxidative stress. Spliced... ]]> Yiting Li http://iris.lib.neu.edu/pharm_sci_theses/24 http://iris.lib.neu.edu/pharm_sci_theses/24 Wed, 27 Mar 2013 10:20:33 PDT The Cannabinoid 1 receptor (CB1) is a type A G-protein coupled receptor (GPCR) expressed most widely in the human brain and has been identified as a key receptor in modulating a number of physiological functions of the human body. Therefore, drugs acting on the CB1 have an enormous pharmacotherapeutic potential in disease conditions such as chronic neuropathic pain, cardio-metabolic diseases, obesity, and even in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In order to develop CB1-specific, high-affinity ligands, a better understanding of the structural aspects of the receptor in its native state is essential. Using an E. coli-based... ]]> Srikrishnan Mallipeddi http://iris.lib.neu.edu/pharm_sci_theses/23 http://iris.lib.neu.edu/pharm_sci_theses/23 Tue, 26 Mar 2013 09:58:11 PDT Currently, tumor-cell resistance to the chemotherapy is key reason for failure of the clinical treatment of cancer cells; almost all chemotherapeutic strategies used are susceptible to multidrug resistance (MDR). The development of MDR is major hindrance to eradication of cancer as it interferes with the effect of therapeutic agents on tumors and increases chances of cancer resurgence.

MDR refers to a cross-resistance to structurally and functionally unrelated drugs thereby rendering the tumor unresponsive to most chemotherapeutic options. It results from microenvironmental selection, like poor delivery efficiency of drug at the disease site, phenotypic alterations in cancer cells leading to enhanced... ]]> Darshna Rajendrakumar Patel http://iris.lib.neu.edu/pharm_sci_theses/22 http://iris.lib.neu.edu/pharm_sci_theses/22 Wed, 29 Aug 2012 06:29:33 PDT Over the last few decades, cancer chemotherapy has advanced by leaps and bounds and yet cancer has been incurable so far. Cancer, uncontrolled growth of cells, depends on several mechanisms for its proliferation and inhibition of cell death. These processes confer unique properties on the cancer. Even though several unique cytotoxic drugs are available and combination therapies are employed, tumor cells are able to survive in many cases. The tumors develop resistance to most of the therapies rendering the cytotoxic drugs ineffective. Moreover, the chemotherapy tends to cause serious side-effects. As a result, a drug delivery system needs to be... ]]> Bhushan Samir Pattni http://iris.lib.neu.edu/pharm_sci_theses/21 http://iris.lib.neu.edu/pharm_sci_theses/21 Mon, 06 Feb 2012 05:52:27 PST National Cancer Institute (NCI) predicts the number of cancer cases in United States alone by the year 2030 to be 2.3 million which is a 45% increase than the current 1.6 million. Therefore there is an undying need for research and development to aggressively attack this disease. Cancer is a multifaceted disease. So, there is no single approach to the treatment of this disease. Various expeditions have been undertaken in all directions to counter this deadly enemy.

Radiation therapy is one of these expeditions. X Rays were discovered by William Roentgen in 1895. The use of radiation therapy began in... ]]> Apurva Kulkarni Doxorubicin Radiation-sensitizing agents Image-guided radiation therapy Nanoparticles http://iris.lib.neu.edu/pharm_sci_theses/20 http://iris.lib.neu.edu/pharm_sci_theses/20 Thu, 12 Jan 2012 07:26:12 PST Despite significant advances in new drug discoveries and treatment combinations, the mortality rate due to cancer has not changed significantly over the last fifty years in the United States and many parts of the world. The inability to detect cancer in its early stage accounts for the lethality, which is then associated with poor prognosis as a result of dissemination to other
organs. In breast cancer, for instance, current therapeutic strategies fail to remove root cause of the diseased. This is largely because of the insufficient accumulation of chemotherapeutic agents into the tumor site upon systemic administration and micro environmental selection... ]]> Hardip Gopani Chemotherapy Cancer - Treatment http://iris.lib.neu.edu/pharm_sci_theses/19 http://iris.lib.neu.edu/pharm_sci_theses/19 Tue, 09 Aug 2011 05:40:12 PDT The aim of this study is to prepare and characterize polymer drug-conjugate delivery system loaded with doxorubicin and melphalan for successful passive or active targeting of these anti-cancer agents to the tumor environment by the enhanced permeability and retention effect and targeted tumor drug delivery. The polymers will be investigated in in vitro cell cultures of various cancers.

The preliminary study in this research focuses on preparation and characterization of polymer-drug conjugates. Doxorubicin and melphalan constitute the model chemotherapeutic agents for conjugation because doxorubicin exhibits maximum absorbance at 490nm where as melphalan exhibits maximum absorbance at 260nm. This difference in... ]]> Savitri Mandapati Cancer - Treatment Drug delivery systems http://iris.lib.neu.edu/pharm_sci_theses/18 http://iris.lib.neu.edu/pharm_sci_theses/18 Tue, 22 Mar 2011 09:46:13 PDT Background: As tumor mass grows beyond a few millimeters in diameter, the angiogenic "switch" is turned on leading to recruitment of blood vessels from surrounding artery and veins. However, the tumor mass is poorly perfused and there are pockets of hypoxia or lower oxygen concentrations relative to normal tissue. Hypoxia-inducing factor-1a (HIF-1a), a transcription factor, is activated when the oxygen concentration is low. Upon activation of HIF-1a, a number of other genes also turn on that allows the tumor to become more aggressive and resistant to therapy.

Purpose: The main objectives of this study were to evaluate the effect of... ]]> Shruti Shah Tumors Neovascularization Metastasis http://iris.lib.neu.edu/pharm_sci_theses/17 http://iris.lib.neu.edu/pharm_sci_theses/17 Tue, 01 Mar 2011 06:22:20 PST Purpose:Multi-compartmental delivery systems can effectively deliver therapeutic payloads by overcoming different extra- and intra-cellular barriers. The main objective of this study was to develop DNA-encapsulated solid nanoparticles-in-emulsion formulation to enhance gene delivery and transfection in macrophages.

Methods:Type B gelatin based nanoparticles were prepared by ethanol water solvent displacement method. Safflower oil-containing water in oil in water multiple emulsion was prepared by a two step emulsification technique with the help of Silverson homogenizer L4RT®. EGFP-N1 plasmid DNA that expresses enhanced green fluorescent protein (GFP) was encapsulated in solid type B gelatin nanoparticles (GNP) which were further encapsulated in the innermost aqueous... ]]> Husain Attarwala Immunology Genetics Emulsions (Pharmacy) Gene therapy Macrophages Nanoparticles Transfection http://iris.lib.neu.edu/pharm_sci_theses/16 http://iris.lib.neu.edu/pharm_sci_theses/16 Wed, 16 Feb 2011 09:49:27 PST It has been previously reported that an organized extracellular matrix can be produced in vitro under serum free conditions from neonatal human dermal fibroblasts cultured without using a three dimensional artificial scaffold. These constructs resemble the human dermis and produce large amounts of hyaluronic acid (hyaluronate, HA). According to previous studies documented in the literature, hyaluronate synthesis and regulation in human dermal fibroblasts is hormonally controlled. We have studied the effects of the hormones Hydrocortisone and Triiodothyronine (T3) on HA and extracellular matrix synthesis, as these hormones are present in the base culture media used to prepare these constructs. We... ]]> Madhura S Deshpande Medical sciences Extracellular matrix Hyaluronic acid Hydrocortisone Triiodothyronine http://iris.lib.neu.edu/pharm_sci_theses/15 http://iris.lib.neu.edu/pharm_sci_theses/15 Fri, 03 Dec 2010 07:47:44 PST The aim of this study was to prepare and characterize Deferoxamine mesylate (DFO) loaded liposomal formulations for targeted delivery to specific organs such as the liver and heart and also to increase the circulation time of DFO in the body for enhanced delivery for potential treatment of iron toxicity. Liposomes which have been extensively studied in the last few decades are spherical lipid vesicles having one or more phospholipid bilayers encapsulating an aqueous core containing the active drug. The preliminary study of this research focuses on optimization of the method for preparation of small unilamellar vesicles and physical characterization of... ]]> Parita T. Ghia Medical sciences Deferoxamine Liposomes http://iris.lib.neu.edu/pharm_sci_theses/14 http://iris.lib.neu.edu/pharm_sci_theses/14 Wed, 06 Oct 2010 05:54:34 PDT The objective of this thesis research is to study the distribution and metabolism of ethanol in the brain using radiolabeled ethanol. This can explain toxicological, pharmacokinetic and pharmacodynamic aspects of alcohol. The brain distribution patterns of [1-14C]ethanol and [2-14C]ethanol treated mice were found different which indicates the differences in the Krebs cycle activity in different brain regions. Earlier studies had shown differences in radioactivity distribution patterns between mice treated with [1-14C]acetaldehyde and mice treated with [1-14C]ethanol. However, the distribution patterns were observed similar in mice pretreated with disulfiram and in control mice. Moreover, hippocampus of mice treated with 100 mg/kg... ]]> Dipankumar C. Patel Medical sciences Ethanol Metabolism Krebs cycle Alcohol--Toxicology http://iris.lib.neu.edu/pharm_sci_theses/13 http://iris.lib.neu.edu/pharm_sci_theses/13 Fri, 10 Sep 2010 10:12:17 PDT Mucins are heavily glycosylated glycoproteins that form a thick layer (glycocalyx) through which all molecules must diffuse to gain access to intracellular targets. They are overexpressed in cancerous conditions and have been implicated in invasion and metastasis of variety of tumors. Over 85% of human cancers are solid tumors in which the effectiveness of cancer therapy depends on adequate delivery of the therapeutic agent to tumor cells. Inadequate delivery would result in residual tumor cells, which in turn could lead to the re growth of tumors and the development of resistant cells. It has recently been shown that pre-exposing human... ]]> Aalok A. Shah Drug delivery systems Cancer--Treatment Mucins--Analysis http://iris.lib.neu.edu/pharm_sci_theses/11 http://iris.lib.neu.edu/pharm_sci_theses/11 Fri, 18 Dec 2009 08:19:14 PST Periodontitis is a chronic inflammatory disease of the periodontal tissues, which can lead to tooth loss and significant sub-gingival tissue deformities. The inflammatory process is initiated by chronic infection resulting from the presence of multi-species bacterial biofilms (dental plaques). Mechanical removal of the periodontal biofilms with or without antimicrobial agents is the current method of treatment. Antiseptics and antibiotics are also used. However, development of resistance in the target organisms is a problem associated with the use of such agents. On the other hand, Porphyromonas gingivalis is a microorganism present in dental plaque and a key player in the development... ]]> Niraj B. Patel Pharmaceutical technology http://iris.lib.neu.edu/pharm_sci_theses/12 http://iris.lib.neu.edu/pharm_sci_theses/12 Fri, 18 Dec 2009 08:19:14 PST We tried to obtain distribution maps of good quality for mouse brain sections for 14C after injecting [1-14C]acetate and [1-14C]acetaldehyde using vibratome/phosphorimager technique. Quantitative analysis of the images obtained with this technique showed significant differences in relative radioactivity between acetaldehyde and acetate in the hippocampus, with acetate levels higher than acetaldehyde. To confirm the results, microdissection experiments of mice brains were conducted, and radioactivity was quantified using liquid scintillation counting. The results were normalized to total brain radioactivity for each radiotracer and significantly higher hippocampus to whole brain ratio was confirmed for acetate compared to acetaldehyde. In contrast to the... ]]> Shachi R. Bhatt Pharmaceutical technology http://iris.lib.neu.edu/pharm_sci_theses/10 http://iris.lib.neu.edu/pharm_sci_theses/10 Fri, 18 Dec 2009 08:19:13 PST The last century has witnessed dramatic advances in targeted delivery of therapeutic molecules. Current drug delivery approaches have successfully achieved tissue-specific and even cell-specific delivery of therapeutic molecules. However, in many cases such advances have resulted in less than the expected dramatic improvement in drug action. It is likely that in such cases, in spite of cell specific delivery, the drug molecules were not successfully delivered to their sub-cellular target inside the cell. It would appear reasonable that for the desired improvement in biological action of such a drug it is necessary to control the sub-cellular distribution of the drug... ]]> Niravkumar R. Patel Pharmaceutical technology http://iris.lib.neu.edu/pharm_sci_theses/9 http://iris.lib.neu.edu/pharm_sci_theses/9 Fri, 18 Dec 2009 08:19:12 PST Mucins are cell surface glycoproteins with protective functions. They are over-expressed in a variety of cancerous conditions. In addition to protection, lubrication and signal transduction functions they have long been implicated in the invasion, metastasis, poor prognosis and extremely poor survival of cancer patients. This exaggerated expression of mucin isoforms in tumor cells is accompanied by their aberrant O-glycosylation. Although O-glycosylation inhibitors have previously been predominantly used to study mucin structure, function and biosynthesis, it has recently been shown that pre-exposing human pancreatic cancer cells with O-glycosylation inhibitors significantly enhances the cytotoxic effects of 5-FU in pancreatic cancer cells. This... ]]> Shweta A. Raina Pharmaceutical technology http://iris.lib.neu.edu/pharm_sci_theses/7 http://iris.lib.neu.edu/pharm_sci_theses/7 Fri, 18 Dec 2009 08:19:11 PST ATC (Anaplastic thyroid cancer) and MTC (medullary thyroid cancer) account for 1-2% and 5-10% of all thyroid cancer cases, respectively. These also represent the most metastatic forms of thyroid cancer. The 5-year survival rate for metastatic MTC is around 40%, while ATC is known to have one of the most dismal prognoses amongst all cancers with 5-year survival rates from 1-7%. Currently, the main treatment options for thyroid cancer are restricted to surgery, radioiodine therapy and external radiation. However, these two forms of thyroid cancer are somewhat radio-resistant and are unable to concentrate radioiodine. No effective chemotherapy options are thus... ]]> Aditi Jhaveri Pharmaceutical technology http://iris.lib.neu.edu/pharm_sci_theses/8 http://iris.lib.neu.edu/pharm_sci_theses/8 Fri, 18 Dec 2009 08:19:11 PST Glioblastoma multiforme (GBM) is an aggressive form of primary brain tumor that afflicts as many as 12,000 patients per year in the United States. GBM is a very aggressive disease and the average patient life-span is reduced to 6 months after diagnosis. Some of the clinical challenges in GBM include difficulty in initial diagnosis, presence of tumor cell ""islets"" in the critical areas of the brain, and the role of blood-brain barrier (BBB) in effective transport and distribution of drugs in the brain. Due to the presence of tumor cell islets, complete surgical resection is not always possible. Additionally, poor... ]]> Sindhura Ganga Pharmaceutical technology http://iris.lib.neu.edu/pharm_sci_theses/6 http://iris.lib.neu.edu/pharm_sci_theses/6 Fri, 18 Dec 2009 08:19:10 PST We aim to prepare a novel drug delivery system by loading nanoliposome therapeutics in human red blood cells (RBCs) by electroporation, and to enhance drug circulation profiles in vivo. During our rigorous evaluation of our delivery approach, we determined that the specific type and concentration of liposomes, as well as the number of electroporation pulses used are important considerations for efficient loading of nanosystems in RBCs. We also investigated the role of a cell preservative solution on the viability of electroporated red blood cells, in an effort to increase the life span of the cells following reinjection. Anionic liposomes were... ]]> Amrita Mehta Pharmaceutical technology