Pharmaceutics and Drug Design Commons^™

Pegylated Nanostructured Lipid Carries For Amphotericin B Ocular Delivery, Prit Manish Lakhani

Electronic Theses and Dissertations

The Chapter II focuses on formulation of an optimized and robust amphotericin B ocular formulation with prolonged precorneal residence and ocular tissue concentration at par or superior to the marketed preparations. Additionally, demonstrating stability of amphotericin B formulations in presence of preservative in comparison to marketed preparation, making it an ideal choice of formulation for multi-dosing. As mentioned earlier, we optimized PEGylated nanostructured lipid carriers (PEG-NLC-AmB) for ocular delivery of amphotericin B. The formulations could be autoclaved with at least one-month stability and in vivo ocular biodistribution was statistically insignificantly different compared to AmBisome®. To accomplish the aim, strategies such …

Drug Repositioning Based On Bounded Nuclear Norm Regularization, Mengyun Yang, Huimin Lao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Computational drug repositioning is a cost-effective strategy to identify novel indications for existing drugs. Drug repositioning is often modeled as a recommendation system problem. Taking advantage of the known drug–disease associations, the objective of the recommendation system is to identify new treatments by filling out the unknown entries in the drug–disease association matrix, which is known as matrix completion. Underpinned by the fact that common molecular pathways contribute to many different diseases, the recommendation system assumes that the underlying latent factors determining drug–disease associations are highly correlated. In other words, the drug–disease matrix to be completed is low-rank. Accordingly, …

Comparative Characteristics Of Antibacterial Activity Of Plants Growing In The Central Part Of The Republic Of Tajikistan., Saidbeg Satorov, F. Mirzoeva, Sh. Satorov, M. Vakhidova, Vyacheslav Dushenkov

Publications and Research

Objective: To evaluate the spectrum of antibacterial activity of plants growing in the central part of the Republic of Tajikistan.
Methods: The antibacterial properties of 18 plant species from the 14 families were studied. The extract samples on dry filter discs were prepared according to the method developed at Rutgers University. Screens-to-Nature (STN) and disc diffusion (DD) methods were used to assess antimicrobial properties of the extracts. The antimicrobial activity of plant extracts was determined against four types of pathogenic standard museum strains of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, as well as …

Regulatory Gaps In Drug Compounding: Implications For Patient Safety, Innovation, And Fraud, Joanna Shepherd

Faculty Articles

Drug compounding is the practice of mixing, combining, or altering drug ingredients to create a product that meets the medical needs of a patient whose needs cannot otherwise be met with commercially-available products. Compounding is essential for patients that are allergic to certain ingredients or cannot tolerate the route of administration or dosage form of a commercially-available drug. Compounding may also enable pharmacists to supply medications when there is a shortage of commercially-available drugs. For example, amid the nationwide shortage of generic liquid Tamiflu and growing flu deaths in early 2018, pharmacists around the country used Tamiflu capsules to compound …

Phase Behavior Of Amorphous Solid Dispersions: Miscibility And Molecular Interactions, Kanika Sarpal

Theses and Dissertations--Pharmacy

Over the past few decades, amorphous solid dispersions (ASDs) have been of great interest to pharmaceutical scientists to address bioavailability issues associated with poorly water-soluble drugs. ASDs consist of an active pharmaceutical ingredient (API) that is typically dispersed in an inert polymeric matrix. Despite promising advantages, a major concern that has resulted in limited marketed formulations is the physical instability of these complex formulations. Physical instability is often manifested as phase heterogeneity, where the drug and carrier migrate and generate distinct phases, which can be a prelude to recrystallization. One important factor that dictates the physical stability of ASDs is …

Pharmacokinetic And Pharmacodynamic Evaluation Of Cocaine Hydrolases For The Treatment Of Cocaine Overdose And Cocaine Addiction Using Rodent Models, Xirong Zheng

Theses and Dissertations--Pharmacy

Overdose and addiction are two medical complications of cocaine abuse. To date, there is no FDA approved pharmacotherapy specific for cocaine abuse. Cocaine hydrolases (CocHs) have been extensively investigated for its potential in anti-cocaine therapy. Previous studies have demonstrated that CocHs efficiently hydrolyze cocaine to generate biologically inactive metabolites both in vivo and in vitro. However, it has not been studied whether there is gender difference in the therapy using CocHs. In addition, the effectiveness of CocHs is unknown for treating cocaine toxicity when alcohol is co-administered.

The main purpose of this dissertation is to characterize and evaluate efficient …

Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel

Theses and Dissertations--Pharmacy

Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.

The goals of …

Discovery Of Novel Pharmacotherapeutics For Substance Use Disorders, Na-Ra Lee

Theses and Dissertations--Pharmacy

Substance use disorders are serious health concerns in the United States. Furthermore, the National Survey on Drug Use and Health reports a continuous increase in substance use disorders in the United States during the last 10 years. However, there are not many effective pharmacotherapeutics available for substance use disorders. The current dissertation is focused on research aimed at discovering pharmacotherapeutics for substance use disorders. First part of dissertation focused on discovering methamphetamine (METH) use disorder therapeutics targeting specific mechanism of METH action on dopaminergic neurons. The second part of dissertation focused on opioids and cocaine use disorder therapeutics targeting rewarding …

Investigation Of Factors Influencing Protein Stability In Lyophilized Formulations Using Solid-State Nmr Spectroscopy, Ashley Lay-Fortenbery

Theses and Dissertations--Pharmacy

Many proteins are unstable in solution and must be formulated in the solid state. This has led to an increase in the use of lyophilized dosage forms. Lyophilization is a complicated processing method consisting of three major steps: freezing, primary drying, and secondary drying. This can lead to several formulation stability challenges including changes in ionization within the matrix, phase separation of the protein drug from added stabilizers, sufficient mobility within the system for movement of reactive species and protein side chains, and crystallization of excipients upon storage. Solid-State Nuclear Magnetic Resonance Spectroscopy (SSNMR) is used to characterize many important …

Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction, Ahmed Hamish Neamah Al-Darraji

Theses and Dissertations--Pharmacology and Nutritional Sciences

Introduction: Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Induced by cardiomyocyte death, MI initiates a prolonged and uncontrolled inflammatory response which impairs the healing process. Immune cells, such as macrophages, play a central role in organizing the early post-MI inflammatory response and the subsequent repair phase. Two activation states of macrophages have been identified with distinct and complementary functions (inflammatory vs. reparatory). This bimodal pattern of macrophage activation is an attractive therapeutic target to favorably resolve post-MI inflammation and enhance recovery. It has been demonstrated that azithromycin (AZM), a commonly used antibiotic with immunomodulatory effects, …

Synthesis Of N-Heterocyclic Molecules And Their Applicability Towards Ion Sensing: Polymeric Chemosensors, Aikohi M. Ugboya

College of Graduate Studies: Theses & Dissertations

Critical to biological and environmental processes are anions because often times their relative concentration in our body can be an indicator of one’s well-being. Therefore, highly sensitive and cost-efficient methods for ions recognition is necessary for human health. In recent times, polymeric chemosensors have become a vital tool for sensing ions because of its higher sensitivity and good mechanical properties compared to their monomeric counterparts. These sensors are designed to produce a measurable response in the presence of a targeted ion such as an electrochemical or optical signal. The unique structure and the photophysical properties of the 1,2,3-triazole core coupled …

Safety Constraint Optimization Of Combination Drug Therapy In Hypertension Clinical Trials, Victor Chukwu

College of Graduate Studies: Theses & Dissertations

In Clinical Practice, combination drug therapy has become common in treating many disease conditions. The purpose of these combinations is often to ensure optimal efficacy and to reduce adverse effects that may arise from monotherapy. Clinical trials have also been conducted to ensure efficacy and safety of these combinations before they are introduced into the market. However, adverse effects still occur with combination therapies. The objective of this study is to (1) To determine a region of optimum doses of Drug A and Drug B in combination while focusing on efficacy alone (2) To determine a region of optimum doses …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

A Hybrid Molecule Of Melatonin And Curcumin For Therpeutic Use In Pulmonary Fibrosis, Varsha V. Nair

Theses and Dissertations

Pulmonary fibrosis (PF) is a serious lung disease, as its life expectancy is only 3-5 years upon occurrence and more than 50 % of the cases are idiopathic, i.e., unknown cause. Two drugs, pirfenidone (PIR) and nintedanib, have recently been approved; however, their efficacies are moderate without evidence of prolonged survival. While this is primarily due to our insufficient knowledge about key PF pathogenesis, inductions of oxidative stress and transforming growth factor-b1 (TGF-b1) have been suggested in PF lungs. Hence, anti-oxidative melatonin (MEL) and curcumin (CUR) have been studied yet their efficacies remain moderate without clear understanding about the mechanisms …

Development Of Multiple Microemulsion Eye Drops For Sustained Release Of New Glaucoma Drug, Doaa Nabih Ahmed Maria

Theses and Dissertations (ETD)

Persistent or repeated elevation of intraocular pressure (IOP) is a primary risk factor of visual field loss in glaucoma, therefore IOP reduction is the first-line therapeutic option in the disease management. Unfortunately, the current therapies are associated with a lot of deficiencies including several daily dosing, reduced efficacy and systemic side effects all of which resulted in poor patient compliance. Previously we have identified Calcium voltage-gated channel auxiliary subunit Alpha2delta 1 gene (Cacna2d1) as a novel modulator of IOP and confirmed that pregabalin targeted CACNA2D1 in eye tissues (ciliary body and trabecular meshwork) to lower IOP in a …

Genetic Exploration Of Hereditary Immune Diseases, Cheng Tian

Theses and Dissertations (ETD)

An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases, rheumatoid arthritis and systemic sclerosis are two of them. My study focuses on these two diseases. Our hypothesis is that mutated genes lead to autoimmune diseases that cause the immune system to attack the human body. The mutated genes cause the gene expression levels to change which fail to properly regulate the body's functions, resulting in immune system diseases. I used existing mouse models to improve the understanding of these two diseases.

The first …

Efficacy And Renal Outcomes Of Sglt2 Inhibitors In Patients With Type 2 Diabetes And Chronic Kidney Disease, Michael S. Kelly, Jelena Lewis, Ashley M. Huntsberry, Lauren Dea, Ivan Portillo

Pharmacy Faculty Articles and Research

Objective: To review glucose-lowering efficacy and changes in renal function associated with sodium-glucose co-transporter 2 (SGLT2) inhibitors among patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).

Data sources: A literature search of MEDLINE and Cochrane databases was performed from 2000 to August 2018 using search terms: SGLT2 inhibitors, sodium glucose co-transporter 2, canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, and chronic kidney disease. References of identified articles were also reviewed.

Study selection and data extraction: English-language studies investigating glucose-lowering endpoints and/or changes in renal function with one of four U.S. approved SGLT2 inhibitors were included. A …

Non-Genomic Effects Of Glucocorticoids: An Updated View, Reynod A. Panettieri, Dedmer Schaafsma, Yassine Amrani, Cynthia Koziol-White, Rennolds S. Ostrom, Omar Tliba

Pharmacy Faculty Articles and Research

Glucocorticoid (GC) anti-inflammatory effects generally require a prolonged onset of action and involve genomic processes. Because of the rapidity of some of the GC effects, however, the concept that non-genomic actions may contribute to GC mechanisms of action has arisen. While the mechanisms have not been completely elucidated, the non-genomic effects may play a role in the management of inflammatory diseases. For instance, we recently reported that GCs ‘rapidly’ enhanced the effects of bronchodilators, agents used in the treatment of allergic asthma. In this review article, we discuss (i) the non-genomic effects of GCs on pathways relevant to the pathogenesis …

Synthesis And Antiproliferative Activities Of Doxorubicin Thiol Conjugates And Doxorubicin-Ss-Cyclic Peptide, Shaban Darwish, Neda Sadeghiani, Shirley Fong, Saghar Mozaffari, Parinaz Hamidi, Thimanthi Withana, Sun Yang, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Myocardial toxicity and drug resistance caused by drug efflux are major limitations of doxorubicin (Dox)-based chemotherapy. Dox structure modification could be used to develop conjugates with an improved biological profile, such as antiproliferative activity and higher cellular retention. Thus, Dox thiol conjugates, Dox thiol (Dox-SH), thiol-reactive Dox-SS-pyridine (SS = disulfide), and a Dox-SS-cell-penetrating cyclic peptide, Dox-SS-[C(WR)4K], were synthesized. Dox was reacted with Traut's reagent to generate Dox-SH. The thiol group was activated by the reaction with dithiodipyridine to afford the corresponding Dox-SS-Pyridine (Dox-SS-Pyr). A cyclic cell-penetrating peptide containing a cysteine residue [C(WR)4K] was prepared using Fmoc solid-phase strategy. Dox-SS-Py was …

Modulation Of Hypoxia-Induced Chemoresistance To Polymeric Micellar Cisplatin: The Effect Of Ligand Modification Of Micellar Carrier Versus Inhibition Of The Mediators Of Drug Resistance, Hoda Soleymani Abyaneh, Amir Hassan Soleimani, Mohammad Reza Vakili, Rania Soudy, Kamaljit Kaur, Francesco Cuda, Ali Tavassoli, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(-carboxyl-"-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and …