Hugh David Charles Smyth

Hugh David Charles Smyth
University of Texas at Austin | UT · Division of Pharmaceutics

Ph.D.

About

245
Publications
49,390
Reads
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4,266
Citations
Additional affiliations
August 2009 - July 2016
University of Texas at Austin
Position
  • Professor (Associate)
January 2007 - present
Lovelace Respiratory Research Institute
Position
  • Professor (Associate)
January 2005 - July 2009
University of New Mexico
Position
  • Professor (Assistant)
Education
January 1998 - November 2000
University of Otago
Field of study
  • Drug Delivery
January 1992 - November 1995
University of Otago
Field of study
  • Pharmacy

Publications

Publications (245)
Article
Tuberculosis (TB) remains a major cause of morbidity and mortality, particularly in low- and middle-income countries where access to health care workers, cold-chain storage, and sterile water sources may be limited. Inhaled drug delivery is a promising alternative to systemic delivery of antimycobacterial drugs, as it enables rapid achievement of h...
Article
Twin-screw extruders are useful in tuning certain product characteristics due to the ability to greatly modify screw profiles as well as operating parameters. However, their use has not yet been applied to dry powder inhalation. In this study the feasibility of using a twin-screw extruder to blend dry powders for inhalation was assessed. Micronized...
Chapter
Poor aqueous solubility of new chemical entities presents various challenges in the development of effective drug delivery systems for various delivery routes. Poorly soluble drugs that are delivered orally may commonly result in low bioavailability and are often subject to considerable food effects. In addition, poorly soluble drugs intended for p...
Article
The process of solids mixing is applied across a considerable range of industries. Pharmaceutical science is one of those industries that utilizes solids mixing extensively. Specifically, solids mixing as a key factor in the preparation of dry powder inhalers using the ordered mixing process will be discussed here. This review opens with a history...
Article
Despite the fact that capsules play an important role in many dry powder inhalation (DPI) systems, few studies have been conducted to investigate the capsules’ interactions with respirable powders. The effect of four commercially available hydroxypropyl methylcellulose (HPMC)inhalation-grade capsule types on the aerosol performance of two model DPI...
Article
Full-text available
Hypertension is a chronic pathology where blood pressure levels are continuously high, causing cardiac, renal, cerebral, and vascular damage leading to early morbi-mortality. This illness is the main risk factor for cardiovascular diseases and the main cause of atrial fibrillation. Atenolol (AT) is a β-1 blocker drug useful for antihypertension and...
Chapter
The respiratory tract is considered an excellent delivery route for local and noninvasive administration of active ingredients, even when its anatomy and physiology may represent an obstacle for drug delivery. This chapter presents the anatomical and physiological characteristics of the airways relevant to the design of drugs and the formulation an...
Article
Full-text available
Capsule-based dry powder inhalers (cDPIs) are widely utilized in the delivery of pharmaceutical powders to the lungs. In these systems, the fundamental nature of the interactions between the drug/formulation powder, the capsules, the inhaler device, and the patient must be fully elucidated in order to develop robust manufacturing procedures and pro...
Article
Monoclonal antibody (mAb) based therapies may provide a valuable new treatment modality for acute and chronic lung diseases, including asthma, respiratory infections, and lung cancer. Currently mAbs are delivered via systemic administration routes, but direct delivery to the lungs via the inhaled route could provide higher concentrations at the sit...
Article
Certain pulmonary diseases, such as cystic fibrosis (CF), non-CF bronchiectasis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia, are usually accompanied by respiratory tract infections due to the physiological alteration of the lung immunological defenses. Recurrent infections may lead to chronic infection through the fo...
Article
Gene therapy and more recently, gene editing is attractive via pulmonary delivery for enhanced regional targeting. However, processing of sensitive therapeutics into dry powders for inhalation can be problematic due to relatively stressful spraying or milling steps. Thin-film freezing-drying (TFFD) has attracted attention with its promising applica...
Article
Full-text available
Introduction Respiratory infections are a major cause of morbidity and mortality. As an alternative to systemic drug administration, inhaled drug delivery can produce high drug concentrations in the lung tissue to overcome resistant bacteria. The development of inhaled fixed-dose combination powders (I-FDCs) is promising next step in this field, as...
Article
Full-text available
Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, administration of the currently available oral formulation results in systemic drug levels that are too low for the inhibition of SARS-CoV-2. We hypothesized that the co-formu...
Chapter
There continues to be a growing need for treatments of central nervous system diseases such as neurodegenerative disease. A significant obstacle to the treatment of central nervous system diseases is the blood-brain barrier. Over the last several decades, the intranasal route of delivery has been reported to provide a bypass of the blood-brain barr...
Article
Lipid nanoparticles are increasingly used for drug and gene delivery, including the delivery of small interfering RNA (siRNA). Pulmonary delivery of drug molecules carried by lipid nanoparticles directly into the lung may improve the treatment of certain lung diseases. The present study was designed to test the feasibility of engineering aerosoliza...
Article
Full-text available
Nanocrystalization technologies have a great potential to substantially increase solubility as well as alleviate the erratic bioavailability behaviour of a range of poorly water soluble drugs. The current study aimed to fabricate smart nanocrystals of lumefantrine (LF) using wet milling technology (DENA DM-100) with the subsequent in vitro, in vivo...
Article
Full-text available
Messenger RNA is a class of promising nucleic acid therapeutics to treat a variety of diseases, including genetic diseases. The development of a stable and efficacious mRNA pulmonary delivery system would enable high therapeutic concentrations locally in the lungs to improve efficacy and limit potential toxicities. In this study, we employed a Desi...
Preprint
Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, the oral formulation produces systemic drug levels that are too low to inhibit SARS-CoV-2. As an alternative, direct delivery of NIC to the respiratory tract as an aerosol cou...
Article
Chemotherapeutic delivery is limited by inefficient transport across cellular membranes. Here we harnesses the cellular gap junction network to release therapeutic cargos directly into the cell cytosol. Specifically, cell-derived vesicles, termed Connectosomes, contain gap junction transmembrane proteins that open a direct passageway to the cellula...
Article
Adjuvant system 04 (AS04) is in injectable human vaccines. AS04 contains two known adjuvants, 3-O-desacyl-4’-monophosphoryl lipid A (MPL) and insoluble aluminum salts. Data from previous studies showed that both MPL and insoluble aluminum salts have nasal mucosal vaccine adjuvant activity. The present study was designed to test the feasibility of u...
Article
A transdermal drug delivery system (TDDS) is generally designed to deliver an active pharmaceutical ingredient (API) through the skin for systemic action. Permeation of an API through the skin is controlled by adjusting drug concentration, formulation composition, and patch design. A bilayer, drug-in-adhesive TDDS design may allow improved modulati...
Chapter
The ability to manage large data sets in real time has been evolving over the last 50 years. Prior to the advent of rapid, high-capacity computing capabilities, the approach to data analysis had been to develop analytical approximations from which metadata could be derived. As the potential to draw direct inferences from data has increased, a new m...
Chapter
A summary is presented of the concluding observations from previous chapters in which it is noted that complexity underpins chemistry, physicochemical properties, pharmaceutical manufacturing, preclinical observations, and population biology (of clinical relevance) and has implications for machine learning and artificial intelligence. For each of t...
Chapter
Monitoring and control of complex processes involve a number of variables whose interactions are necessarily complex. Unlike many other areas of pharmaceutical development, this has long been recognized by process engineers who have the task of guaranteeing the quality and performance of the product. A variety of statistical, physical, and mathemat...
Chapter
Machine learning (ML) is a field of computer science that allows interrogation to allow modified navigation (learning) of the data and through statistical derivation prediction of unseen data or events. ML has been a high-profile topic for many years and is ubiquitous in many aspects of daily life – from e-mail spam and malware filtering to search...
Chapter
Complex phenomena leading to nonlinear behavior occur at all scales of scrutiny. The underlying complexity in chemical and physicochemical phenomena has been noted. Chemical reactions, molecular aggregation, and self-association have been shown to follow principles that require nonlinear interpretation to allow prediction of system behavior. Some p...
Chapter
The complexity of biological systems is recognized superficially, but there has been a tendency through reductionism to believe that fundamental understanding is achieved through examination of the smallest building blocks of life. There is steadily increasing understanding that looking at large populations particularly as the tools have become ava...
Chapter
The complexity of pharmacokinetics and drug efficacy during clinical development is due to the multiscale understanding required from molecular drug-target interactions to organismal-level phenotypes. Since the first edition of this volume, a steady growth in advanced mathematical and/or computational techniques has been reported in the improved de...
Chapter
Pharmaceutical systems and products almost always include solid-state ingredients either during manufacture or as the dosage form itself. Thus preformulation and formulation of drug products is often critically dependent on the characterization and understanding of these physicochemical properties. Despite their seemingly simplicity, attributes lik...
Article
This review provides an assessment of post-inhalation cough with therapeutic aerosols. Factors that increase cough may be mitigated through design of the drug, formulation and device. The incidence of cough is typically less than 5% for drugs with a nominal dose less than 1 mg, including asthma and COPD therapeutics. Cough increases markedly as the...
Article
A significant limitation of locally delivered treatments for chronic pulmonary infections is often the short residence time within the airways. Ciprofloxacin (CIP), for example, undergoes rapid absorption from the airway lumen. Previously, we demonstrated that the complexation of CIP with copper (CIP-Cu) reduces its apparent epithelial permeability...
Article
Tuning the composition of antimicrobial nanogels can significantly alter both nanogel cytotoxicity and antibacterial activity. This project investigated the extent to which PEGylation of cationic, hydrophobic nanogels altered their cytotoxicity and bactericidal activity. These biodegradable, cationic nanogels were synthesized by activators regenera...
Article
Therapeutic delivery of drug and gene delivery systems have to traverse multiple biological barriers to achieve efficacy. Mucosal administration, such as pulmonary delivery in cystic fibrosis (CF) disease, remains a significant challenge due to concentrated viscoelastic mucus, which prevents drugs and particles from penetrating the mucus barrier. T...
Article
Full-text available
Background: Novel methods are necessary to reduce morbidity and mortality of patients suffering from infections with Pseudomonas aeruginosa. Being the most common infectious species of the Pseudomonas genus, P. aeruginosa is the primary Gram-negative etiology responsible for nosocomial infections. Due to the ubiquity and high adaptability of this...
Article
In contrast to the plethora of antibacterial agents, only a handful of antifungals are currently available to treat Candida albicans biofilm-associated infections. Additional novel antibiofilm strategies to eliminate C. albicans biofilm infections are needed. This study aims to improve the efficacy of a widely used azole, fluconazole by co-deliveri...
Article
For carrier-based dry powder inhaler (DPI) formulations, the adhesion between carrier particles and active pharmaceutical ingredients (API) particles have a significant influence on the aerosolization performance of the API-carrier complexes and the desired detachment of the API for efficient pulmonary delivery. In our previous study, nano-porous m...
Book
Non-linear phenomena pervade the pharmaceutical sciences. Understanding the interface between each of these phenomena and the way in which they contribute to overarching processes such as pharmaceutical product development may ultimately result in more efficient, less costly and rapid implementation. The benefit to Society is self-evident in that a...
Chapter
This chapter provides an overview of the factors that are considered in dosage form design, including physicochemical properties of drugs, drug solubility and dissolution, drug bioavailability, membrane permeability, and solid-state characteristics. Commonly performed preformulation studies including dissolution testing, X-ray diffraction, thermogr...
Chapter
This chapter provides an introductory overview on concepts related to drug delivery to the lungs. Physiological barriers to lung delivery are examined, as are the mechanisms for overcoming these barriers through delivery device and formulation design. A review is provided of delivery mechanisms and design of the three major classes of pulmonary dru...
Chapter
This chapter expands upon the concept of drug solubility and dissolution as it relates to dosage form design. Excipients utilized in solution-based dosage forms and parenteral products are discussed in detail, including solvents, cosolvents, antioxidants, preservatives, complexing agents, and surfactants. Special considerations which must be made f...
Chapter
This chapter covers the fundamentals of nasal drug delivery. Anatomical barriers to drug delivery, examples and functions of commonly used excipients, and device design are reviewed. Analytical procedures relevant to testing the performance of nasal drug products are also introduced.
Chapter
This chapter reviews numerous concepts relevant to drug delivery topically and transdermally. Topics covered include the skin’s function barrier, mechanisms for drug transport through the skin, in vitro analytical techniques, and methods to increase drug permeation. Commonly used formulation approaches such as semisolid dosage forms and transdermal...
Chapter
This chapter presents an extensive overview of the concepts of delayed-release, sustained-release, and pulsatile-release for drug delivery. Formulation approaches and delivery technologies are discussed in detail, along with the required performance testing for modified-release dosage forms. Abuse-deterrent technologies are also introduced.
Chapter
This chapter provides an overview of dosage forms relevant to rectal and vaginal drug delivery. Barriers to drug absorption are discussed and frequently used excipients are covered. The manufacturing and special formulation considerations for drug delivery using suppository formulations are also reviewed.
Chapter
This chapter covers crucial aspects of the formulation of pharmaceutical suspensions. Properties relevant to suspension stability and drug delivery are discussed, including particle settling, flocculation, particle aggregation, viscosity, zeta potential, and Ostwald ripening are discussed. Methods of particle size reduction are introduced, includin...
Chapter
This chapter provides a guide on how to implement a flipped-classroom model into a pharmaceutics course. Course design, daily class organization, strategies for student success, and how to implement prereading materials (specifically this text) are discussed in detail.
Chapter
This chapter provides an overview of emulsion types, their methods for manufacture, and their suitability for various routes of administration. Excipients and their function in promoting emulsion stability are discussed. A review of microemulsions and liposomes is also provided.
Chapter
This chapter introduces special considerations and formulation techniques for ophthalmic and otic drug delivery. Types of ophthalmic dosage forms are reviewed and placed in clinically relevant context. Commonly used excipients and their functions are also reviewed.
Chapter
This chapter provides an overview of the design, manufacturing, and formulation of capsule and tablet-based drug products. Manufacturing methods for producing both capsules and tablets are extensively discussed, and figures are incorporated to aid student understanding. Frequently used excipient categories are provided along with general functions...
Article
Pulmonary delivery of biopharmaceuticals may enable targeted local therapeutic effect and noninvasive systemic administration. Dry powder inhaler (DPI) delivery is an established patient-friendly approach for delivering large molecules to the lungs; however, the complexities of balancing protein stability with aerosol performance require that the d...
Article
Nose-to-brain delivery has gained significant interest over the past several decades. This has resulted in numerous strategies described to improve the delivery of drugs to the brain directly through the olfactory epithelium of the nasal cavity. In some cases, intranasal administration may be more effective than other routes of administration in tr...
Preprint
Mucus is an impregnable barrier for drug delivery across the epithelia for treatment of mucosal-associated diseases. While current carriers are promising for mucus penetration, their surface chemistries do not possess chemical complexity to probe and identify optimal physicochemical properties desired for mucus penetration. As initial study, we use...
Preprint
Full-text available
Drugs and drug delivery systems have to traverse multiple biological barriers to achieve therapeutic efficacy. In diseases of mucosal-associated tissues such as cystic fibrosis (CF), successful delivery of gene and drug therapies remains a significant challenge due to an abnormally concentrated viscoelastic mucus, which prevents ~99% of all drugs a...
Article
This paper describes the design of stimuli-sensitive theranostic nanoparticles, composed of reduced graphene oxide (rGO) self-assembled on thermosensitive liposomes encapsulated doxorubicin (DOX) and carbon quantum dot (CQD) (CQD-DOX-rGO-Tlip). The rGO-Tlip particles have been observed to be flower-shaped objects. The thermoresponsive and theranost...
Article
Full-text available
There is a current need to develop and optimize new therapeutics for the treatment of dental caries, but these efforts are limited by the relatively low throughput of relevant in vitro models. The aim of this work was to bridge the 96-well microtiter plate system with a relevant multispecies dental caries model that could be reproducibly grown to a...
Article
A limitation of antibiotic treatments for P. aeruginosa (PA) chronic pulmonary infections is the reduced efficacy due to sub-therapeutic concentrations at the infection site and the development of biofilm. A novel approach to sustain ciprofloxacin (CIP) in the lungs after inhalation is to reduce its pulmonary absorption rate by its complexation wit...
Article
Franz cell (FC) experiments in topical and transdermal drug development represent the gold standard in vitro method but require a relatively high quantity of human skin, are low-throughput, and are time-consuming to perform. To address these issues, we studied a micro-well plate-based screening method for permeability and retention that could enabl...
Article
Full-text available
Biofilm infections have gained recognition as an important therapeutic challenge in the last several decades due to their relationship with the chronicity of infectious diseases. Studies of novel therapeutic treatments targeting infections require the development and use of models to mimic the formation and characteristics of biofilms within host t...
Article
Orally inhaled products have well-known benefits. They allow for effective local administration of many drugs for the treatment of pulmonary disease, and they allow for rapid absorption and avoidance of first-pass metabolism of several systemically acting drugs. Several challenges remain, however, such as dosing limitations, low and variable deposi...
Book
Particularly in healthcare fields, there is growing movement away from traditional lecture style course towards active learning and team-based activities to improve learning and build higher level thinking through application of complex problems with a strong foundation of facts and data. Essential Pharmaceutics is suited to this modern teaching st...
Article
Chitosan has been widely employed to deliver nucleic acids such as siRNA and plasmids. However, chitosan-mediated delivery of gene-editing system has not been reported yet. In this study, poly(ethylene glycol) monomethyl ether (mPEG) was conjugated to chitosan with different molecular weights (low molecular weight and medium molecular weight chitos...
Article
Although high-speed laser imaging is the current standard to characterize the plume angle of suspension-based pressurized metered dose inhalers (pMDIs), this method is limited by the inability to identify the drug content in a droplet and simulate inhalation flow. The Plume Induction Port Evaluator (PIPE) is a modified induction port for cascade im...
Article
The objective of this work is to use phage display libraries as a screening tool to identify peptides that facilitate transport across the mucus barrier. Mucus is a complex selective barrier to particles and molecules, limiting penetration to the epithelial surface of mucosal tissues. In mucus-associated diseases such as cystic fibrosis (CF), mucus...
Article
Full-text available
Photothermal therapy with various nanoparticles, as photothermal transducers, is a widely researched technique. A continuous wave (CW) laser is employed during this procedure. The therapeutic setup is slightly modified to measure the optical absorption cross-section of the graphene oxide (GO), by mitigating the effects of heat diffusion and light s...
Article
For the last several decades, the predominant method for delivering medicine to the surface of the eye has been the standard multiuse eye dropper. While being the most popular, this method has significant limitations. Recently, an effort has been made to explore the use of a directed toroidal vortex or "smoke ring" aerosol delivery system that may...
Article
The number of biologics in the therapeutic development pipeline is increasing including those delivered though inhalation (Morales, 2017; Fathe, 2016). Biologics comprise a broad variety of complex macromolecules with unique physicochemical characteristics. These distinctive characteristics control their pharmacological mechanisms of action, stabil...
Article
The present studies were designed to evaluate inhalatory microparticles carrying indomethacin (IN) for potential local (specific and non-specific bronchial inflammatory asthma responses) and systemic treatments (joint inflammation, rheumatoid arthritis and osteoarthritis pain) by optimizing microparticle properties, characterizing their lung deposi...
Patent
Full-text available
The present invention relates to inhalable microparticles loaded with a fluoroquinolone/metal cation complex which enable sustained fluoroquinolone lung exposure. Advantageously these inhalable microparticles sustain the fluoroquinolone in the pulmonary epithelial lining fluid (ELF) by decreasing the fluoroquinolone apparent permeability across the...
Article
There is currently no in vitro technique for assessing plume geometry of nasal sprays under airflow conditions. However, a majority of FDA approved nasal products recommend that patients inhale during actuation. Therefore, a reproducible in vitro test that measures plume angles under physiologically relevant inhalation flow rates would be useful. T...
Article
Full-text available
Glioblastoma multiforme (GBM) is the most common and lethal central nervous system tumor. Recently, atovaquone has shown inhibition of signal transducer and activator transcription 3, a promising target for GBM therapy. However, it is currently unable to achieve therapeutic drug concentrations in the brain with the currently reported and marketed f...
Article
Delivery of drugs to the lungs via dry powder inhaler (DPI) is a promising approach for the treatment of both local pulmonary conditions and systemic diseases. Though DPIs are widely used for the pulmonary deposition of potent bronchodilators, anticholinergics, and corticosteroids, there is growing interest in the utilization of this delivery syste...