Medicinal-Pharmaceutical Chemistry Commons^™

Theranostic Nanoparticles Folic Acid-Carbon Dots-Drug(S) For Cancer, Godwin Kweku Babanyinah

Electronic Theses and Dissertations

This study aims to prepare theranostic nanoparticles (NPs) that are expected to increase cancer diagnostics and therapeutic efficacy. We prepared the NPs constituting carbon dots (CDs) as an imaging agent, folic acid as a targeting agent, doxorubicin (DOX), or gemcitabine (GEM) as chemotherapy agents. The NPs include noncovalent FA-CDs-DOX, covalent CDs-FA-DOX, and covalent FA-CDs-GEM. Through ultraviolet-visible spectroscopy, fluorescence spectroscopy, and Fourier transform-infrared spectroscopy, the fabrication of these NPs was confirmed. It was discovered that the high drug loading efficiency is the noncovalent series while the high drug loading capacity is the covalent series The in-vitro pH-dependent drug release data indicate …

Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza

Graduate Theses and Dissertations

The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …

Structure Formation And Coupling Reactions Of Hexaphenylbenzene And Its Brominated Analog, Jacob D. Teeter, Paulo S. Costa, Christoph Dobner, Mamun Sarker, Alexander Sinitskii, A Enders

Department of Chemistry: Faculty Publications

The on-surface coupling of the prototypical precursor molecule for graphene nanoribbon synthesis, 6,11-dibromo-1,2,3,4-tetraphenyltriphenylene (C₄₂Br₂H₂₆, TPTP), and its non-brominated analog hexaphenylbenzene (C₄₂H₃₀, HPB), was investigated on coinage metal substrates as a function of thermal treatment. For HPB, which forms non-covalent 2D monolayers at room temperature, a thermally induced transition of the monolayer’s structure could be achieved by moderate annealing, which is likely driven by π-bond formation. It is found that the dibrominated carbon positions of TPTP do not guide the coupling if the growth occurs on a substrate at temperatures that …

Data For "Subtype-Selective Positive Modulation Of Sk Channels Depends On The Ha/Hb Helices", Miao Zhang, Meng Cui

Pharmacy Faculty Data Sets

In the activated state of small-conductance Ca²⁺-activated potassium (SK) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates SK2a and SK3 channel activity but not the SK1 and IK subtypes. Here, we report that the subtype-selectivity of CyPPA relies on the HA/HB helices. Mutating residues in the HA (V420) and HB (K467) helices of SK2a channels to their equivalent residues in IK channels diminished the potency of CyPPA. CyPPA elicited prominent responses on mutant IK channels with an arginine residue in the HB helix substituted for its equivalent lysine residue in the SK2a channels …

Effective Microwave-Assisted Approach To 1,2,3-Triazolobenzodiazepinones Via Tandem Ugi Reaction/Catalyst-Free Intramolecular Azide–Alkyne Cycloaddition, Maryna O. Mazur, Oleksii S. Zhelavskyi, Eugene M. Zviagin, Svitlana V. Shishkina, Vladimir I. Musatov, Maksim A. Kolosov, Elena H. Shvets, Anna Yu. Andryushchenko, Valentyn A. Chebanov

Department of Chemistry: Faculty Publications

A novel catalyst-free synthetic approach to 1,2,3-triazolobenzodiazepinones has been developed and optimized. The Ugi reaction of 2-azidobenzaldehyde, various amines, isocyanides, and acids followed by microwave-assisted intramolecular azide–alkyne cycloaddition (IAAC) gave a series of target heterocyclic compounds in moderate to excellent yields. Surprisingly, the normally required ruthenium-based catalysts were found to not affect the IAAC, only making isolation of the target compounds harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes

Sulfur Anions: Comments Upon Structure, Charles A. Kingsbury

Department of Chemistry: Faculty Publications

This work emphasizes the need for solvent simulation as well as a counterion in calculations concerning anions, although optimization may be difficult. Solvent and counterion both play a large role in conformation of the ion. Part of the reason for the success of sulfur anions in chemical reactions may be the ability of sulfone oxygen(s) to coordinate with the counterion (usually lithium). The “solvent” partially dissociates lithium from the carbanion center.

Identifying Receptors For Neuropeptides And Peptide Hormones: Challenges And Recent Progress, Md Shadman Ridwan Abid, Somayeh Mousavi, James W. Checco

Department of Chemistry: Faculty Publications

Intercellular signaling events mediated by neuropeptides and peptide hormones represent important targets for both basic science and drug discovery. For many bioactive peptides, the protein receptors that transmit information across the receiving cell membrane are not known, severely limiting these signaling pathways as potential therapeutic targets. Identifying the receptor(s) for a given peptide of interest is complicated by several factors. Most notably, cell-cell signaling peptides are generated through dynamic biosynthetic pathways, can act on many different families of receptor proteins, and can participate in complex ligand-receptor interactions that extend beyond a simple one-to-one archetype. Here, we discuss recent methodological advances …

Using Molecular Dynamics Simulations To Understand Receptor-Complex Communication And Signaling, Hannah Margaret Hoag

Theses and Dissertations

The overarching purpose of this document is to use Computer-aided drug design and Molecular dynamic simulations to better understand elusive drug-receptor interactions, as well as various types of inter-receptor signaling. Chapter One introduces the theory and importance of Computer-aided drug design and the methodology used in both Chapters Two and Three.

Chapter Two uncovers the relationship between the well-studied ABCB1 transporter and a newly identified drug known as Xanthohumol (XN). XN is compared to a commonly used drug, Doxorubicin (DOX), in this chapter. If the ABCB1 transporter can be properly inhibited, cancer-fighting drugs will be able to stay within the …

Label‑Free Spectral Imaging To Study Drug Distribution And Metabolism In Single Living Cells, Qamar Alshammari, Rajasekharreddy Pala, Nir Katzir, Surya M. Nauli

Pharmacy Faculty Articles and Research

During drug development, evaluation of drug and its metabolite is an essential process to understand drug activity, stability, toxicity and distribution. Liquid chromatography (LC) coupled with mass spectrometry (MS) has become the standard analytical tool for screening and identifying drug metabolites. Unlike LC/MS approach requiring liquifying the biological samples, we showed that spectral imaging (or spectral microscopy) could provide high-resolution images of doxorubicin (dox) and its metabolite doxorubicinol (dox’ol) in single living cells. Using this new method, we performed measurements without destroying the biological samples. We calculated the rate constant of dox translocating from extracellular moiety into the cell and …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Synthesis And Cytotoxicity Of Trisubstituted Imidazoles, Venkata Agasthya Kasibotla

Theses and Dissertations

Aza heterocyclic compounds are an important class of organic compounds that play a major role in medicinal chemistry. Majority of the heterocyclic motifs such as imidazoles, triazoles, piperazines etc. act as building blocks for synthesizing active pharmaceutical ingredients. Several pharmaceutical drugs include these motifs due to their varying physicochemical properties, which enable them to exhibit wide range of pharmacological activities ranging from anti-fungal, anti-neoplastic, anti-helmintic, anti-microbial etc. Owing to their electron rich ring system, imidazole and piperazine based motifs have become an attractive target for design and development of novel chemical structures as new drugs. In the current study, we …

Differential Modulation Of Sk Channel Subtypes By Phosphorylation, Young-Woo Nam, Dezhi Kong, Dong Wang, Razan Orfali, Rinzhin T. Sherpa, Jennifer Totonchy, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated K⁺ (SK) channels are voltage-independent and are activated by Ca²⁺ binding to the calmodulin constitutively associated with the channels. Both the pore-forming subunits and the associated calmodulin are subject to phosphorylation. Here, we investigated the modulation of different SK channel subtypes by phosphorylation, using the cultured endothelial cells as a tool. We report that casein kinase 2 (CK2) negatively modulates the apparent Ca²⁺ sensitivity of SK1 and IK channel subtypes by more than 5-fold, whereas the apparent Ca²⁺ sensitivity of the SK3 and SK2 subtypes is only reduced by ∼2-fold, when heterologously …

Structure Formation And Coupling Reactions Of Hexaphenylbenzene And Its Brominated Analog, Jacob D Teeter, Paulo S. Costa, Christoph Dobner, Mamun Sarker, Alexander Sinitskii, Axel Enders

Department of Chemistry: Faculty Publications

The on-surface coupling of the prototypical precursor molecule for graphene nanoribbon synthesis, 6,11-dibromo-1,2,3,4-tetraphenyltriphenylene (C₄₂Br₂H₂₆, TPTP), and its non-brominated analog hexaphenylbenzene (C₄₂H₃₀, HPB), was investigated on coinage metal substrates as a function of thermal treatment. For HPB, which forms non-covalent 2D monolayers at room temperature, a thermally induced transition of the monolayer’s structure could be achieved by moderate annealing, which is likely driven by π-bond formation. It is found that the dibrominated carbon positions of TPTP do not guide the coupling if the growth occurs on a substrate at temperatures that …

Convergent Synthesis Of Anaephene B, Megan Johnson

Honors Program Theses

Many organisms are capable of producing organic compounds as secondary metabolites; these natural products can be quite pharmaceutically and medicinally relevant.1 Typically, the more unique an organism, the more unique its secondary metabolites. Cyanobacteria, an abundant microalgal organism, is capable of producing a myriad of novel natural products.2 The unique photosynthetic and autotrophic properties of cyanobacteria allow for the production of many secondary metabolites, including lipopeptides, amino acids, fatty acids, macrolides, amides, and others.2,3 Staphylococcus aureus is one the most common bacterial infections in the world.4 S. aureus produces a number of metabolites that inhibit host immune responses.4 As a …

Analysis Of Sexual Lubricants As A Form Of Trace Evidence For Sexual Assault Cases, Brooke Baumgarten

Electronic Theses and Dissertations, 2020-2023

A major gap in sexual assault casework is demonstrated when DNA is not recovered. Oftentimes, if DNA evidence is not present on the collection swabs, the sexual assault kit (SAK) is not further analyzed. Due to the "CSI effect," DNA is commonly understood as highly identifiable evidence, potentially leading to increased condom usage to eliminate or reduce DNA transfer during a sexual assault. Therefore, the analysis of condoms and sexual lubricants is pertinent. The purpose of this research is to develop analytical protocols to potentially connect unknown substances recovered in a SAK to known lubricant reference samples. Sexual lubricants were …

Philippine Medicinal Plants With Potential Immunomodulatory And Anti-Sars-Cov-2 Activities, Fabian M. Dayrit, Armando M. Guidote Jr, Nina Gloriani, Sheriah Laine M. De Paz-Silava, Irene M. Villaseñor, Rene Angelo S. Macahig, Mario A. Tan, John Ross N. Chua, Isidro C. Sia

Chemistry Faculty Publications

Coronavirus disease 2019 (COVID-19) continues to devastate the world’s health and economy, affecting all aspects of life leading to widespread social disruption. Even as several vaccines have been developed, their availability in developing countries is limited and their efficacy against the variants of SARS-CoV-2 (severe acute respiratory syndrome–coronavirus 2) needs to be continuously assessed. The World Health Organization (WHO) has acknowledged that vaccines alone will not overcome the global challenges of COVID-19. Medicinal plants may provide the needed support. Herein, we identify Philippine medicinal plants that possess phytochemicals with potential anti-SARS-CoV-2 activity and/or immunomodulatory properties that may strengthen one’s immune …

Fine-Tuning Of Molecular Structures To Generate Carbohydrate Based Super Gelators And Their Applications For Drug Delivery And Dye Absorption, Jonathan Bietsch, Mary Olson, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-based low molecular weight gelators (LMWGs) exhibit many desirable properties making them useful in various fields including applications as drug delivery carriers. In order to further understand the structural connection to gelation properties, especially the influence of halide substitutions, we have designed and synthesized a series of para-chlorobenzylidene acetal protected D-glucosamine amide derivatives. Fifteen different amides were synthesized, and their self-assembling properties were assessed in multiple organic solvents, as well as mixtures of organic solvents with water. All derivatives were found to be gelators for at least one solvent and majority formed gels in multiple solvents at concentrations lower than …

Bisphosohoglycertae Mutase: A Potential Target For Sickle Cell Disease, Anfal S. Aljahdali

Theses and Dissertations

Bisphosphoglycerate mutase (BPGM) is a part of the erythrocyte glycolysis system. Specifically, it is a central enzyme in the Rapoport-Leubering pathway, a side glycolytic pathway involved in the regulation of the concentration of the natural allosteric effector of hemoglobin (Hb), 2,3-bisphosphoglycerate (2,3-BPG). BPGM catalyses the synthesis and hydrolysis of 2,3-BPG through its synthase and phosphatase activities. The synthase activity is the main role of BPGM, while the phosphatase activity is low and is activated by the physiological effector, 2-phosphoglycolate (2-PG) with the latter mechanism poorly understood.

BPGM activity and 2,3-BPG levels in red blood cells (RBCs) have a significant role …

Peroxo Species Formed In The Bulk Of Silicate Cathodes, Zhenlian Chen, Bjoern Schwartz, Xianhui Zhang, Wenqiang Du, Lirong Zheng, Ailing Tian, Ying Zhang, Zhiyong Zhang, Xiao Cheng Zeng, Zhifeng Zhang, Liyuan Huai, Jinlei Wu, Helmut Ehrenberg, Deyu Wang, Jun Li

Department of Chemistry: Faculty Publications

Oxygen redox in Li-rich oxides may boost the energy density of lithium-ion batteries by incorporating oxygen chemistry in solid cathodes. However, oxygen redox in the bulk usually entangles with voltage hysteresis and oxygen release, resulting in a prolonged controversy in literature on oxygen transformation. Here, we report spectroscopic evidence of peroxo species formed and confined in silicate cathodes amid oxygen redox at high voltage, accompanied by Co2+/Co3+ redox dominant at low voltage. First-principles calculations reveal that localized electrons on dangling oxygen drive the OO dimerization. The covalence between the binding cation and the O-O dimer determines the degree of electron …

Dynamic Manipulation Of Droplets Using Mechanically Tunable Microtextured Chemical Gradients, Ali J. Mazaltarim, John J. Bowen, Jay M. Taylor, Stephen Morin

Department of Chemistry: Faculty Publications

Materials and strategies applicable to the dynamic transport of microdroplets are relevant to surface fluidics, self-cleaning materials, thermal management systems, and analytical devices. Techniques based on electrowetting, topographic micropatterns, and thermal/chemical gradients have advanced considerably, but dynamic microdroplet transport remains a challenge. This manuscript reports the fabrication of mechano-tunable, microtextured chemical gradients on elastomer films and their use in controlled microdroplet transport. Specifically, discreet mechanical deformations of these films enabled dynamic tuning of the microtextures and thus transport along surface-chemical gradients. The interplay between the driving force of the chemical gradient and the microtopography was characterized, facilitating accurate prediction of …

Recent Advances In Supramolecular Affinity Separations: Affinity Chromatography And Related Methods, Ashley G. Woolfork, Sazia Iftekhar, Susan Ovbude, Kyungah Suh, Sadia Sharmeen, Isaac Kyei, Jacob Jones, David S. Hage

David Hage Publications

Contents

1 Introduction

2 Supports for Affinity Chromatography

 2.1 Natural Supports and Related Materials

 2.2 Inorganic Supports

 2.3 Synthetic Supports

 2.4 Magnetic Beads and Particles

 2.5 Smart Materials

 2.6 Nanomaterials

 2.7 Support Formats

3 Immobilization Methods

 3.1 Non-Covalent Immobilization

 3.2 Covalent Immobilization

4 Binding Agents Used in Affinity Chromatography

 4.1 Biological Agents as Affinity Ligands

4.1.1 Immunoaffinity Chromatography

4.1.2 Immunoglobulin-Binding Proteins

4.1.3 Lectins

4.1.4 Enzymes

4.1.5 Serum Proteins

4.1.6 Biotin, Avidin, and Streptavidin

4.1.7 Carbohydrates

4.1.8 Lipids

4.1.9 Nucleic Acids

 4.2 Non-Biological Agents as Affinity Ligands

4.2.1 Boronates and Related Mixed Ligands

4.2.2 Dye-Ligands

4.2.3 Immobilized Metal-Ion Chelates

4.2.4 Molecularly …

Using Nmr Spectroscopy And Computational Chemistry To Confirm The Structure Of Novel Antibiotic Nocamycin O, Stephanie Lewis

CMC Senior Theses

In recent years, many medically promising antibiotics have been discovered in nature, especially in insect-microbe symbioses. One of the better-studied examples of this kind of defensive relationship is that of fungus-growing ants and the antibiotic-producing Actinobacteria. These bacteria produce several defensive chemicals with myriad uses, including one antibiotic that inhibits the growth of several bacterial strains, including other Actinobacteria. This antibiotic (known as nocamycin O) is a promising candidate for medicinal use due to its similarities to bacterial RNA polymerase inhibitors tirandamycin and streptolydigin, which inhibit several human pathogens. The determination of the structure of nocamycin O will be an …

Enabling Technologies For Medicinal Chemistry And Synthesis: I. Cannabinoids; Ii. Illudalic Acid; Iii. Microwave Chemistry, Harvey Fulo

Graduate Theses, Dissertations, and Problem Reports (ETD)

Innovations in synthetic organic chemistry such as methodology improvements, new chemical transformations and technology development significantly impact medicinal chemistry and continue to drive the drug discovery process. Here, new cyclization strategies to the pharmaceutically underexplored 3,3-dimethylcyclopentane-fused aromatic rings are described. One approach highlighted oxidative cycloisomerization, intermolecular [2+2+2] cyclotrimerization and 5-exo-dig cyclization providing indanoylindole cannabinoids that possess high affinity for human CB₂ receptors at nanomolar concentration and good selectivity index. Another featured a [4+2]-type benzannulation reaction which enabled the 5-step synthesis of illudalic acid — compared to the current available sequences (≥16 steps) — and its equipotent and LAR-selective analogs. …

Biocompatible And Multifunctional Trityl Spin Probes For Electron Paramagnetic Resonance Spectroscopy, Teresa D. Gluth

Graduate Theses, Dissertations, and Problem Reports (ETD)

The primary objective of my thesis was to develop and utilize a biocompatible multifunctional trityl spin probe for concurrent measurement of pO₂, pH_e, and [P_i] in vivo by electron paramagnetic resonance (EPR) spectroscopy (Chapter 2). My first goal was to synthesize the proposed probe we are terming HOPE71. Secondly, HOPE71 was characterized by X-band and L-band EPR spectroscopy. Next, the biocompatibility of HOPE71 was assessed through an albumin binding test, cytotoxicity assays, and in vivo intravenous tolerance. Then, the use of HOPE71 to measure the target parameters was demonstrated in a breast cancer …

Rational Design Of Small Molecule Disruptors Of Protein-Protein Interactions: Pd-1/Pd-L1; C-Myc, Arid4b, Samuel Ofori

Theses and Dissertations--Chemistry

Protein-protein interactions (PPIs) are vital to many biological processes, including gene expression, and immune reactions to pathogens. There are approximately 650,000 PPIs in humans with pertinent physiological functions. Aberrant expression of PPIs lead to improper function and contribute to a plethora of disease conditions including cancer. Thus, PPIs represent an enormous target space for drug discovery and chemical probes. Direct targeting of clinically relevant PPIs with small molecules remains an unmet medical need. Development of small-molecule inhibitors of PPIs is a challenging enterprise and in most cases considered undruggable due to large protein surfaces, lack of deep binding pockets and …

Design, Synthesis, And Anticancer Properties Of Ru(Ii) Complexes With Organometallic, “Expanded” Bipyridine, And O,O’-Chelating Ligands, Raphael Ryan

Theses and Dissertations--Chemistry

Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. …

Synthesis Of Dual Small Molecule Hybrids To Probe The Synergy Between Dna Repair Enzymes And Ido1, Nathaniel George

Theses and Dissertations--Chemistry

Indoleamine 2 3-dioxygenase (IDO) has recently been highlighted as a promising target for small molecule based immunotherapy. IDO is often coopted by various cancer cells to promote an immune-suppressive environment around tumors. DNA damage repair (DDR) enzymes have recently been targeted for inhibition to promote genetic instability and bolster immune recognition. DDR enzymes such as PARP and POLγ are common inhibition targets due to their direct effects on cellular function. In the process of designing conjugate inhibitors of IDO and DDR enzymes, novel synthetic methodology was developed for the mild deprotection of N-Tert-butyloxycarbonyl (N-BOC) group from various amines. Conjugate …

Computational Insights On Medicinal Chemistry Targeting Cyp450s, Alexander D. Fenton

Theses and Dissertations--Chemistry

Modern-day medicinal chemistry has provided researchers with a wide variety of tools to not only gather greater insight from their data, but also to generate data in new ways. One such tool is the construction of computational protein models from crystallographic datasets, and their subsequent use to understand the structure-activity relationships of protein-ligand complexes. These models can be utilized for their predictive power to inform the synthesis of, and improvement of, lead compounds. It is the goal of this work to employ such models to the CYP450 enzyme system such that potent and selective inhibitors can be designed, evaluated biologically, …

Bayesian-Derived Vancomycin Auc24h Threshold For Nephrotoxicity In Special Populations, Dan Ho

University of the Pacific Theses and Dissertations

A Bayesian-derived 24-hour area under the concentration-time curve over minimum inhibitory concentration from broth microdilution (AUC24h/MICBMD) ratio of 400 to 600 is recommended as the new monitoring parameter for vancomycin to optimize efficacy and minimize nephrotoxicity. The AUC24h threshold of 600 mg*h/L for nephrotoxicity was extrapolated from studies that assessed the general population. It is unclear if this upper threshold is consistent or varies when used in special populations such as critically ill patients, obese patients, patients with preexisting renal disease, and patients on concomitant nephrotoxins.The purpose of this study is to investigate the generalizability of the proposed vancomycin AUC24h …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …