Pharmacy and Pharmaceutical Sciences Commons^™

Nanosuspension Based Electrolyte Sensitive In Situ Gel For Topical Ocular Delivery Of Natamycin, Poorva H. Joshi

Electronic Theses and Dissertations

Natamycin (NT) is a commercially available antifungal drug used for the treatment of fungal keratitis, an infection which affects the clear corneal surface and its associated layers. Currently, NT is available commercially as a 5% w/v ophthalmic suspension, to be administered topically. The main objective of the present investigation was to develop and evaluate the natamycin loaded nanosuspension (NT-NS), as well as it’s corresponding in-situ gel (NT-NS-GG), for the treatment of fungal keratitis. NT-NS was prepared using homogenization technique and optimized based on size, PDI, zeta potential (ZP), assay and process stability. Further, optimized NT-NS was modified into an in-situ …

Formulation Development Of Natamycin Loaded Nanoemulsion For Ocular Drug Delivery, Kanika Goel

Electronic Theses and Dissertations

Natamycin (NT), also known as Pimaricin, is predominantly used as an anti-fungal medication for the treatment of fungal infections around the eye. The goal of the present study was to formulate and optimize NT loaded nanoemulsion (NT-NE) and examine its potential application in ophthalmic drug delivery. Placebos were evaluated with respect to particle size, PDI and ZP to identify the aqueous phase and lipid phase concentrations to be carried forward with NT-NE development. NT-NE were prepared by hot homogenization and ultra-probe sonication method, using Castor oil (CO) and Miglyol 812 as liquid lipids, Tween®80 and Poloxomer 188 as surfactants. NT-NE …

Formulation Strategies To Address Physiological And Anatomical Constraints For Improved Topical Ocular Drug Delivery, Karthik Yadav Janga

Electronic Theses and Dissertations

Delivery of therapeutic molecules to the eye has been a complicated task owing to its anatomical and physiological barriers. This dissertation delineates several formulation strategies to circumvent dynamic and static constraints hampering the ocular drug delivery. Advanced vesicular systems, bilosomes and transfersomes, were prepared to improve the ocular pharmacotherapy of natamycin (NT). NT bilosomes and transfersomes were further loaded into in situ gel systems which transformed immediately to hydrogel, in the simulated tear fluid, with good viscoelastic and mucoadhesive properties.In vitro corneal transport studies confirmed the superior permeability characteristics of NT from the optimized bilosome and transfersome in situ gel …

Development Of Continuous Manufacturing Process Of Acyclovir Ointment Using Hot-Melt Extrusion, Rui Wang

Electronic Theses and Dissertations

Hot-melt extrusion is a viable technology in preparing the pharmaceutical delivery system and has been considered as an attractive alternative to conventional processing methods. The objective of this study was to utilize the advantage of continuous manufacturing in HME to design and evaluate a formulation of topical semisolid ointment. Melt fusion ointments containing 5% of acyclovir (ACV) in water-soluble base with PEG 400, PEG 1500, and PEG 3350 polymers at various ratio were prepared. A design of experiment using I-optimal design was conducted. This design was used to study the influence of polymer ratio on the physicochemical properties of the …

Development Of Topical Oil/Peg Creams Of Voriconazole, Abhishek Shivashankar Shettar

Electronic Theses and Dissertations

Voriconazole (VRC) was selected as a model drug for preparation of Oil/PEG cream consisting of PEG 2000, PEG 400 and propylene glycol after performing drug-excipient compatibility studies. Twin screw processor with a 10 mm co-rotating twin screw configuration was used for preparation of oil/PEG creams. Creams prepared using twin-screw processor were characterized for the following: Differential Scanning Calorimetry (DSC), pH, Solvent activity (as)), viscosity, drug content uniformity, in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) using human cadaver skin. Creams are heterogenous biphasic semi-solid preparations consisting of oil and aqueous phases, wherein one phase is dispersed …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …

Semisynthetic Aurones: A Family Of Newly Discovered Tubulin Inhibitors As Antineoplastic Agents, Yanqi Xie

Theses and Dissertations--Molecular and Cellular Biochemistry

Aurones belong to an uncommon class of plant flavonoids that provide the bright yellow coloration of some ornamental flowers and that possess a range of biological activities. Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the biologically active analogs developed in the course of this dissertation work were (Z …

Developmental Expression Of Monocarboxylate Transporter 1 And 4 In Rat Liver, Michael Ng, Justin Louie, Jieyun Cao, Melanie A. Felmlee

School of Pharmacy Faculty Articles

PURPOSE: Monocarboxylate transporters (MCT) are proton-coupled integral membrane proteins that control the influx and efflux of endogenous monocarboxylates such as lactate, acetate and pyruvate. They also transport and mediate the clearance of drugs such as valproate and gamma-hydroxybutyrate. CD147 functions as ancillary protein that chaperones MCT1 and MCT4 to the cell membrane. There is limited data on the maturation of MCT and CD147 expression in tissues related to drug distribution and clearance. The objective of the present study was to quantify hepatic MCT1, MCT4, and CD147 mRNA, whole cell and membrane protein expression from birth to sexual maturity.

METHODS: Liver …

Hiv Viral Rebound Due To A Possible Drug-Drug Interaction Between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide And Calcium-Containing Products: Report Of 2 Cases, S. Lena Kang-Birken, Dena El-Sayed, John Prichard

School of Pharmacy Faculty Articles

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a potent fixed-dose, once-daily regimen for HIV-1 treatment and has rare emergence of drug resistance. We report a potential drug-drug interaction in 2 female patients both receiving treatment for HIV and cerebral toxoplasmosis: one case between E/C/F/TAF with calcium carbonate and a second case involving leucovorin as calcium salt. Both cases resulted in rise in HIV RNA levels and emergence of M184 V mutation and resistance to elvitegravir and raltegravir. To the best of our knowledge, these 2 cases are the first reports of rapid emergence of mutation from coadministration of E/C/F/TAF and calcium.

Responsible, Safe, And Effective Use Of Biologics In The Management Of Low Back Pain: American Society Of Interventional Pain Physicians (Asipp) Guidelines, Annu Navani, Laxmaiah Manchikanti, Sheri L. Albers, Richard E. Latchaw, Jaya Sanapati, Alan David Kaye, Sairam Atluri, Sheldon Jordan, Ashim Gupta, David Cedeno, Alejandro Vallejo, Bert Fellows, Nebojsa Nick Knezevic, Miguel Pappolla, Sudhir Diwan, Andrea M. Trescot, Amol Soin, Adam M. Kaye, Steve M. Aydin, Aaron K. Calodney, Kenneth D. Candido, Sanjay Bakshi, Ramsin M. Benyamin, Ricardo Vallejo, Art Watanabe, Douglas Beall, Todd P. Stitik, Patrick M. Foye, Erik M. Helander, Joshua A. Hirsch

School of Pharmacy Faculty Articles

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public …

Mechanisms Underlying Neuroprotection By The Nsaid Mefenamic Acid In An Experimental Model Of Stroke, Parto S. Khansari, Robert F. Halliwell

School of Pharmacy Faculty Articles

Stroke is a devastating neurological event with limited treatment opportunities. Recent advances in understanding the underlying pathogenesis of cerebral ischemia support the involvement of multiple biochemical pathways in the development of the ischemic damage. Fenamates are classical non-steroidal anti-inflammatory drugs but they are also highly subunit-selective modulators of GABAA receptors, activators of IKS potassium channels and antagonists of non-selective cation channels and the NLRP3 inflammosome. In the present study we investigated the effect of mefenamic acid (MFA) in a rodent model of ischemic stroke and then addressed the underlying pharmacological mechanisms in vitro for its actions in vivo. The efficacy …

Hiv With Opportunistic Neuroinfection, Rahul Vyas, Rajendra Prasad

Digital Journal of Clinical Medicine

No abstract provided.

Anti-Cancer Effects Of Renieramycin T On Human Non-Small Cell Lung Cancer Cells, Korrakod Petsri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Mcl-1 targeted therapy is promising strategy for lung cancer treatment since it is contributed to aggressive lung cancer and chemotherapeutic resistance. At present, many compounds targeting on Mcl-1 are currently under different clinical stages of development for cancer treatment. Herein, we report the Mcl-1 targeting activity of renieramycin T (RT), an alkaloid isolated from the blue sponge Xestospongia sp. RT was shown to target on Mcl-1 through ubiquitin-proteasomal degradation in lung cancer cells including chemotherapeutic resistant primary lung cancer cells. Additionally, RT also affects the activation of p53 and decrease of Bcl-2 which can lead to apoptosis of cancer cells. …

Developing A Rational Peptide Ligand Design Method Using Cd13 As A Prototype Target Receptor, Md Zahir Uddin

University of the Pacific Theses and Dissertations

Structure based computational peptide design methods have gained significant interest in recent years with the availability of structural insights of protein-protein interactions obtained from the crystal structures. Most of these approaches design new peptide ligands by connecting the crucial amino acid residues from the protein interface and are generally not based on any predicted receptor-ligand interaction. In this work, a peptide design method based on the Knob-Socket model was used to identify the specific ligand residues packing into the receptor interface. This method enables rational peptide ligand design by predicting amino acid residues that will fit best at the binding …

Fliposomes With A Ph-Sensitive Conformational Switch For Anticancer Drug Delivery Against Triple Negative Breast Cancer, Yifan Lu

University of the Pacific Theses and Dissertations

Cancer is the second leading cause of death in the US and worldwide, accounting for 16% of deaths worldwide in 2015. Of more than 100 types of cancers affecting humans, breast cancer is the most common cancer among women and is the second leading cause of death in women. Triple negative breast cancer (TNBC) is a subtype of breast carcinomas defined by the lack of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2 /neu). The prognosis and survival of TNBC patients remains the poor due to the lack of effective targeted therapy. …

Synthesis And Conformational Studies Of Various Amides, Marcos Beltran-Sanchez

University of the Pacific Theses and Dissertations

In the past, aminocyclohexanol rings have been successfully utilized as pH-triggered molecular switches in various trans-2-aminocyclohexanol derivatives. By changing the groups on the amine nitrogen, these models provided a wide pH range in which a switch can occur. The pH-induced switch of conformation was monitored by 1H-NMR spectroscopy. The models were also incorporated into the bilayer membrane of liposome structures and tested for their ability to disrupt their membrane upon their conformational flip induced by a decrease in pH.

In this work, the amide bond has been studied as a molecular switch and various amide derivatives have been tested for …

Sheehan Syndrome, Riya Jain, Shashidhara Kc, Savitha Savitha

Digital Journal of Clinical Medicine

No abstract provided.

Ectopia Lentis, Pratheek Prabhu

Digital Journal of Clinical Medicine

No abstract provided.

Cerebro-Vascular Accident, Mehak Gera, Rajendra Prasad, Suresh Babu, Manthappa M

Digital Journal of Clinical Medicine

No abstract provided.

Pulmonary Thromboembolism In A Case Of Alopecia Areata, Rakshith M

Digital Journal of Clinical Medicine

No abstract provided.

Design, Synthesis And Pharmacological Characterization Of Potential Mu Opioid Receptor Selective Ligands, Abhishek S. Kulkarni

Theses and Dissertations

Selective Mu Opioid Receptor (MOR) antagonists possess immense potential in the treatment of opioid abuse/addiction. Utilizing the “message-address” concept, our laboratory reported a novel, reversible, non-peptide MOR selective antagonist 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4՛-pyridyl)carboxamido]morphinan (NAP). Molecular modeling studies revealed that the selectivity of NAP for the MOR is because of a π-π stacking interaction of its pyridine ring with the Trp318residue in theMOR. Pharmacological characterization showed that NAP is a P-glycoprotein substrate, thereby limiting its use in the treatment of opioid abuse/addiction. Thus, to modify NAP, we replaced the pyridine ring with its isosteric counterpart thiophene. Isosteric replacement …

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 …

Impact Of A Primary Care Pharmacist Utilizing A Team-Based Model Of Care, Priya Verma Pharmd, Rachel Steele Pharmd, Bcacp, Ashley Parrott Pharmd, Mba, Bcps, Bcacp

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada / Poster 11-134

Objective: To characterize the impact of a primary care pharmacist working in a team-based care model, by determining: • The acceptance rate for all recommendations • The total number of each recommendation type • The number of referrals to the primary care pharmacist, if the patient was an appropriate candidate for comprehensive medication management

Assessing Appropriateness Of Inpatient Rifaximin Use In A Community Health System, Alissa Keillor Pharmd, Sarah Pfaehler Pharmd, Mba, Bcps, Lorin Yolch Pharmd, Bcgp, Bcac

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada / Poster # 11-135

Objective: To evaluate the appropriateness of inpatient rifaximin use and healthcare resource utilization best-practices within a community health-system.

Impact Of Atypical Antipsychotics On Sedation Requirements In Mechanically Ventilated, Critically Ill Patients, Michael Genday Pharmd, Dustin D Linn Pharmd, Bcps, Bcccp, Jim Roy Pharmd, Bcps, Bcccp

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada

Objective: To determine if atypical antipsychotics lower continuous infusion sedation requirements while also assessing risk

Standardized Approach To Implementation Of Infusion Pump Interoperability, Tara Jellison Pharmd, Mba, Fashp, Rebecca S. Mahuren Bsn, Rn

Parkview Pharmacy Department

2019 ASHP Midyear Clinical Meeting / Las Vegas, Nevada / Poster #708041 08-105

Purpose: Describe the process to implement smart pump–electronic health record (EHR) interoperability technology throughout a multi-facility community health system to improve intravenous (IV) medication safety and efficiency with auto-programming, reducing keystroke errors and edits from 17 step manual process to 7 steps.

The Role Of Aryl Hydrocarbon Receptor (Ahr) In Drug-Drug Interaction And The Expression Of Ahr In Pichia Pastoris, Yujuan Zheng

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor is a ligand-activated transcription factor that is involved in many important functions in the body. To study the role and function of AHR, an abundant amount of in vitro expressed and purified protein is needed. A baculovirus insect expression system is commonly employed to express AHR, however, there are several drawbacks with this method, such as mutation potential and high cost. A better in overexpression system is needed and we hypothesize that Pichia pastoris, a yeast expression system, could stably express AHR and ARNT (aryl hydrocarbon receptor nuclear translocator) in sufficient amount with reasonable cost. Codon …

The Potency Of Ag10 In Stabilizing Transthyretin Is Driven By Interactions Mimicking The Disease-Suppressing T119m Variant, Dengpan Liang

University of the Pacific Theses and Dissertations

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a fatal disease with no available disease-modifying therapies. While destabilizing TTR mutations increase the risk of developing ATTR-CM, the naturally occurring Thr119Met (T119M) variant stabilizes TTR and prevent disease. The two Serine 117 and Serine 117’ (S117/S117’) side chain hydroxyl groups of monomers A and B in T119M variant TTR form direct hydrogen bonds with each other. AG10 is an orally available, small molecule TTR stabilizer in Phase 3 clinical development for ATTR-CM. Structural features that infer high potency of AG10 for stabilizing TTR remains incompletely characterized.

In order to investigate the contribution of …

Development And Characterization Of Ldv Peptide Targeted Nanocarriers For Paclitaxel Delivery: A Comparative Study Of Micelles, Liposomes And Solid Lipid Nanoparticles, Poonam Dattani

University of the Pacific Theses and Dissertations

Nanocarriers have been established as delivery vehicles to target cancer tumors. However, premature drug leakage is one of the major reasons for inefficient drug delivery of nanocarriers to the tumor. Drug diffusion out of the nanocarriers or destabilization of drug loaded nanocarriers by physiological interactions with blood cells, serum proteins, and cell membranes upon systemic administration contribute to premature drug release. In this study, targeted micelles, liposomes and solid lipid nanoparticles (SLNs) of similar composition were prepared and characterized to compare physicochemical characteristics, in vitro stability, in vitro release rates in release media and in vivo performance. Peptide Amphiphiles (PAs) …

Lipid-Coated Magnesium Phosphate Nanoparticles For Intrapulmonary Protein Delivery In Mice, Mallika Vadlamudi

University of the Pacific Theses and Dissertations

Proteins are a diverse category of biomolecules with great therapeutic potential. Intracellular delivery of proteins can augment the deficient activities of dysfunctional or poorly expressed innate proteins and therefore represents a promising strategy to treat the associated diseases. One major barrier to intracellular protein delivery is the translocation of the protein across the cellular membrane. Endocytosis provides an important pathway for protein nanocarriers to enter cells across the plasma membrane. However, the cargo protein must then promptly escape from the endosomes to avoid degradation in the lysosome and to exert its cellular function.

Previously, we reported a cationic lipid-coated magnesium …