Michael Roberts

• The University of Queensland

Background Propanil toxicity is characterised by severe prolonged methaemoglobinaemia, cyanosis, acidosis, and progressive end-organ dysfunction. In vitro studies report propanil-induced kidney toxicity, which has not been studied clinically. This study determined the incidence of acute kidney injury and of methaemoglobinaemia after propanil self-p...

Introduction: Propranolol is a beta-adrenoceptor blocking drug with sodium channel-blocking properties that can cause life-threatening toxicity in overdose. Limited research defines dose thresholds of toxicity. We aimed to investigate propranolol overdose and dose thresholds for severe toxicity. Material and methods: This is a prospective series...

Purpose Typical clinical “in use” conditions for topical semisolids involve their application as a thin film, often with rubbing that can induce metamorphic stress. Yet, product quality and performance tests often characterize the manufactured product, and may not consider product metamorphosis (e.g., shear history) during dispensing and administra...

Purpose The objective of this study was to investigate whether different dispensing processes can alter the physicochemical and structural (Q3) attributes of a topical cream product, and potentially alter its performance. Methods Acyclovir cream, 5% (Zovirax®) is sold in the UK and other countries in a tube and a pump packaging configurations. The...

Background The combination of intravenous hydrocortisone and enteral fludrocortisone may reduce mortality in patients with septic shock. The optimal dose and reliability of absorption of fludrocortisone in critically ill patients are unclear. Methods In a multi-centre, open label, phase II randomized clinical trial, intravenous hydrocortisone alon...

Introduction: Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasm...

Purpose To develop a toolkit of test methods for characterizing potentially critical quality attributes (CQAs) of topical semisolid products and to evaluate how CQAs influence the rate and extent of active ingredient bioavailability (BA) by monitoring cutaneous pharmacokinetics (PK) using an In Vitro Permeation Test (IVPT). Methods Product attribu...

Chemical excipients used in topical formulations may be toxic to living skin cells. Here, we compared the in vitro toxicity of some common solubilizing excipients against human melanoma cells, human keratinocytes (HaCaT) and primary skin fibroblasts (FB) as examples of cancerous, immortalized and primary human skin cells, often used as experimental...

It is common for people to be exposed to multiple topical products daily, either through cosmetics, personal care or drug formulations. This increases the possibility of contact dermatitis and poses a major challenge for treatment as well as the design and regulation of safe and effective topical products. Here, we define the scope of the problem o...

With increasing global focus on planetary boundaries, food safety and quality, the presence of per- and polyfluoroalkyl substances (PFAS) in the food chain presents a challenge for the sustainable production and supply of quality assured food. Consumption of food is the primary PFAS exposure route for the general population. At contaminated sites,...

The presence of esterase enzymes in human skin and their role in drug metabolism has been reported, but their distribution in the various skin layers and the relative contributions of those layers to metabolism is poorly defined. To gain further insight into esterase distribution, we performed in vitro skin permeation of a commercial 28.3% methyl s...

The migration of per- and polyfluoroalkyl substances (PFAS) onto agricultural properties has resulted in the accumulation of PFAS in livestock. The environmental determinants of PFAS accumulation in livestock from the grazing environment are poorly understood, resulting in limited capacity to manage livestock exposure and subsequent transfer of PFA...

Seborrheic dermatitis (SD) is a common dermatological disorder with symptoms that include skin flaking, erythema and pruritus. This review discusses the topical products available for treating SD, which target several aspects of disease pathobiology, including cutaneous microbial dysbiosis (driven by Malassezia yeast), inflammation, sebum productio...

Cell membrane-coated nanoparticles are emerging as a new type of promising nanomaterials for immune evasion and targeted delivery. An underlying premise is that the unique biological functions of natural cell membranes can be conferred on the inherent physiochemical properties of nanoparticles by coating them with a cell membrane. However, the exte...

Warming the skin is a key means of promoting solute permeation through the skin. Changes in solute permeation associated with variations in skin temperature also assist in understanding the mechanism by which solutes permeate the skin. However, few studies have considered the relative impact of temperature on the main determinants of the maximum fl...

The potential exposure to the widely used glyphosate-based herbicides, including attempted suicide by ingestion, is of world-wide concern. Whilst the major focus to date has been on managing exposure to the active ingredient glyphosate, it is now recognised that a common major ‘inert’ surfactant ingredient, polyethoxylated tallow amine (POEA) and r...

Warming of the skin is now an accepted means of promoting skin permeation. Accordingly, the usually quite onerous thermodynamic studies on solute transport through the skin have practical applications. Phenolic compounds permeate through the skin by partitioning into and diffusing through the stratum corneum (SC) intercellular lipids, with their si...

Physiologically based pharmacokinetic (PBPK) modeling has increasingly been employed in dermal drug development and regulatory assessment, providing a framework to integrate relevant information including drug and drug product attributes, skin physiology parameters, and population variability. The current study aimed to develop a stepwise modeling...

Pharmacokinetic (PK) models are widely used to describe drug permeation across the epidermal membrane barrier, the stratum corneum (SC). Here, we extend our previously reported diffusion and compartment-in-series models to describe plasma concentrations, urinary excretion-time profiles and exposure estimates after topically applied finite doses of...

This study examined a number of factors that can impact the outcomes of in vitro human epidermal permeation coefficients for aliphatic alcohols and steroids, including receptor phase composition and study conditions. We determined experimentally the solubilities and IVPT permeation of a homologous series of ¹⁴C labeled aliphatic alcohols (ethanol,...

Recent advances in topical and transdermal drug delivery systems have enabled targeted delivery of therapeutics to the site of action by enhancing drug permeation across the stratum corneum and increased bioavailability. Despite various technological advancements, some dermatoses still have limited treatment options due to potential adverse effects...

This work expands the recently developed compartmental model for skin transport to model variable diffusion and/or partition coefficients, and the presence of slow equilibration/slow binding kinetics within stratum corneum. The model was validated by comparing it with the diffusion model which was solved numerically using the finite element method....

Zinc pyrithione (ZnPT) is a widely used antifungal, usually applied as a microparticle suspension to facilitate delivery into the hair follicles, where it then dissociates into a soluble monomeric form that is bioactive against yeast and other microorganisms. In this study, we use multiphoton microscopy (MPM) and fluorescence lifetime imaging micro...

Purpose The quality testing and approval procedure for most pharmaceutical products is a streamlined process with standardized procedures for the determination of critical quality attributes. However, the evaluation of semisolid dosage forms for topical drug delivery remains a challenging task. The work presented here highlights confocal Raman micr...

The dataset represented in this article is referred to by the review article entitled “Topical drug delivery: history, percutaneous absorption, and product development” (MS Roberts et al., 2021) [1]. The dataset contains maximal flux (Jmax), and permeability coefficient (kp) values collated from In Vitro human skin Permeation Test (IVPT) reports pu...

The skin concentration of a substance after a topical application or exposure determines both local treatment outcomes and the dermal toxicity assessment of various products. However, quantifying the time course of those concentrations at skin effect sites, such as the viable epidermal, superficial dermis and appendages in humans is especially prob...

Background and objectives: Tramadol is commonly prescribed to manage chronic pain in older patients. However, there is a gap in the literature describing the pharmacokinetic parameters for tramadol and its active metabolite (O-desmethyltramadol [ODT]) in this population. The objective of this study was to develop and evaluate a population pharmaco...

This work presented data on pharmacokinetics of tramadol and ODT in older patients

Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP and penetration into the VE is ill-defined. We therefore quantified the...

Liver diseases such as viral hepatitis, cirrhosis, and hepatocellular carcinoma are common in clinical practice with high morbidity and mortality. Various types of nanoparticles (NPs) have been developed and strategically functionalized to embrace multiple imaging and therapeutic techniques for liver disease diagnosis and treatment. These NPs can s...

This chapter introduces the routes of administration of therapeutic and diagnostic compounds to the body, the considerations in designing drug delivery systems, and some examples of the innovations that have contributed new controlled delivery products. In addition to the oral route, the most common nonparenteral routes of delivery are topical/tran...

Zinc pyrithione (ZnPT) is an anti-fungal drug delivered as a microparticle to skin epithelia. It is one of the most widely used ingredients worldwide in medicated shampoo for treating dandruff and seborrheic dermatitis (SD), a disorder with symptoms that include skin flaking, erythema and pruritus. SD is a multi-factorial disease driven by microbio...

PurposeSubcutaneous fentanyl injection is commonly prescribed to manage acute pain in older patients; however, there is a gap in the literature describing the pharmacokinetic parameters for this route of administration in this population. The aim of this study was to develop and evaluate a population pharmacokinetic model for subcutaneous fentanyl...

Topical drug therapy is one of the most effective approaches in third-degree burn wound treatments. To optimize and enhance drug permeation through burn eschar, we need to characterize this barrier, most importantly, its affinity to drugs; the subject of this investigation. Hansen Solubility Parameters (HSP), as polarity and affinity scale, were me...

Topical products, widely used to manage skin conditions, have evolved from simple potions to sophisticated delivery systems. Their development has been facilitated by advances in percutaneous absorption and product design based on an increasingly mechanistic understanding of drug-product-skin interactions, associated experiments, and a quality-by-d...

Although statins are effective in treating high cholesterol, adverse effects do occur with their use. Efficacy and tolerability vary among statins in different ethnic groups. Indigenous Australians have a high risk for cardiovascular and kidney diseases. Prescribing statins to Indigenous Australians with multi-morbidity requires different strategie...

Liver diseases have become an increasing health burden and account for over 2 million deaths every year globally. Standard therapies including liver transplant and cell therapy offer a promising treatment for liver diseases, but they also suffer limitations such as adverse immune reactions and lack of long-term efficacy. Artificial cells that mimic...

Background: The clinical characteristics following self-poisoning with organophosphorus (OP) insecticides differs according to the insecticide ingested. Phenthoate is a dimethoxy WHO Hazard Class II OP pesticide with limited literature on its clinical characteristics and outcome. We aimed to better understand its clinical characteristics by studyi...

Introduction A range of opioids are commonly prescribed to manage chronic pain, but individual patient responses vary greatly, especially in older populations. One source of that variability are differences in absorption, metabolism and excretion, i.e. pharmacokinetics. Blood, plasma and serum concentrations of opioids allow that variability to be...

Background: Pesticide poisoning is among the most common means of suicide globally, but can be prevented with regulation of the most hazardous agents. We aimed to compare the lethality of pesticides ingested by our cohort, seek evidence on variation between human and regulatory animal toxicity, and establish change over time in the case fatality o...

Increasing emphasis is being placed on using in vitro permeation test (IVPT) results for topical products as a surrogate for their in vivo behaviour. This study sought to relate in vivo plasma concentration - time pharmacokinetic (PK) profiles after topical application of drug products to IVPT findings with mechanistic diffusion and compartment mod...

The past decade has seen many advancements in the development of three-dimensional (3D) in vitro models in pharmaceutical sciences and industry. Specifically, organoids present a self-organising, self-renewing and more physiologically relevant model than conventional two-dimensional (2D) cell cultures. Liver organoids have been developed from a var...

Objectives: Orphenadrine is an antihistamine possessing both anticholinergic and sodium channel blocking properties. Orphenadrine overdose has been relatively rare because it has been superseded by better therapeutic alternatives. However, the trend toward utilising non-opioid agents to treat chronic pain has seen a resurgence in the therapeutic us...

Background Opioids are commonly prescribed to managing chronic pain in older persons. However, these patients are often at risk of drug-opioid interactions due to polypharmacy. Objectives To identify the prevalence of opioid prescribing and drug-opioid interactions in poly-medicated older patients and factors associated with opioid prescribing. Set...

The topical delivery route is proposed as an alternative or adjunctive approach to melanoma treatment, since the target site for melanoma treatment-the epidermal basal layer-is potentially accessible by this route. Microemulsion systems are effective delivery vehicles for enhanced, targeted skin delivery. This work investigated the effect of Rose B...

Introduction In the past, mathematical modelling of the transport of transdermal drugs has been primarily focused on the stratum corneum. However, the development of pharmaceutical technologies, such as chemical enhancers, iontophoresis, and microneedles, has led to two outcomes; an increase in permeability in the stratum corneum or the ability to...

Objective The permeation of hydrophilic molecules through the skin is still a challenge due to the barrier posed by stratum corneum, the outermost layer of the skin. Liposomes have frequently been used as carriers for different types of drugs and may also function as permeation enhancers. Propylene glycol has also been used as an edge activator in...

Introduction Skin has been used as an administration route for local or systemic action since ancient times. The efficacy and toxicity of any product applied to the skin is determined by the chemical composition and physicochemical properties of the active(s) and excipients, which in turn govern their percutaneous absorption and effects. Areas cov...

Multiphoton fluorescence lifetime microscopy has revolutionized studies of pathophysiological and xenobiotic dynamics, enabling the spatial and temporal quantification of these processes in intact organs in vivo. We have previously used multiphoton fluorescence lifetime microscopy to characterise the morphology and amplitude weighted mean fluoresce...

Zinc oxide nanoparticles (ZnO NPs) are a key constituent of many commercial broad-spectrum sunscreens. Studies have shown that these nanoparticles are retained on the superficial layers of the skins barrier layer, the stratum corneum (SC), and solubilised zinc species from the ZnO NPs have been shown qualitatively to penetrate intact human skin. Th...

Acetaminophen (APAP) is the foremost cause of drug-induced liver injury in the Western world. Most studies of APAP hepatotoxicity have focused on the hepatocellular injury, but current hepatocyte-related biomarkers have delayed presentation time and a lack of sensitivity. APAP overdose can induce hepatic microvascular congestion, which importantly...

In recent years, the “quality by design” (QbD) approach has been used for developing pharmaceutical formulations. This is particularly important for complex dosage forms such as topical semisolid products. The first step for developing a product using this efficient approach is defining the quality target product profile (QTPP), a list of quality a...

Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and to relate observed trough antibiotic concentrations to optimal targets. Methods: We per...

Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and to relate observed trough antibiotic concentrations to optimal targets. Methods: We perfo...

Hepatocellular carcinoma (HCC) is the most common type of primary tumor in the liver and is a leading cause of cancer‐related death worldwide. Activated hepatic stellate cells (HSCs) are key components of the HCC microenvironment and play an important role in the onset and progression of HCC through the secretion of growth factors and cytokines. Cu...

Background Pain is common in older patients and management guidelines rarely consider the effect of multiple comorbidities and concurrent medications on analgesic selection. Objectives The objectives of this study were to identify the prevalence and pattern of analgesic prescribing and associated factors in older patients with polypharmacy. Metho...

In this work, we developed a number of generalised skin diffusion based pharmacokinetic models to relate published in vivo urinary excretion data to matching experimentally generated in vitro human skin permeation test (IVPT) data for a series of topically applied salicylate esters. A simplified linear in vivo model was found to inadequately descri...

Suspensions of the UV filter, zinc oxide nanoparticles (ZnO NP), are widely used in sunscreen products. This paper compared the relative disposition and local cytotoxicity of ZnO NP, and zinc ions formed on its dissolution, against keratinocyte cultures and in the human epidermis (ex vivo) after application of suspensions of ZnO NP. HaCaT keratinoc...

We describe the contribution of our in vivo multiphoton microscopy (MPM) studies over the last ten years with DermaInspect^® (JenLab, Germany), a CE-certified medical tomograph based on detection of fluorescent biomolecules, to the assessment of possible penetration of nanoparticulate zinc oxide in sunscreen through human skin. At the tim...

Mathematical models are often applied to describe cell migration regulated by diffusible signalling molecules. A typical feature of these models is that the spatial and temporal distribution of the signalling molecule density is reported by solving a reaction-diffusion equation. However, the spatial and temporal distributions of such signalling mol...

This work explored Falls risk associated with opioid use in older patients

This work highlighted the prevalence of opioids adverse effects in older patients

This work investigated the appropriateness of PPI use in older patients

This work highlighted opioid use in polymedicated older patient and risk of DDIs

Acne vulgaris is a common inflammatory pilosebaceous condition that affects 80–90% of adolescents. Since the introduction of tretinoin over 40 years ago, topical retinoid products have been a mainstay of acne treatment. The retinoids are very effective in addressing multiple aspects of the acne pathology as they are comedolytic and anti-inflammator...

We present a new cell membrane modification methodology where the inherent heart tissue homing properties of the infectious bacteria Streptococcus gordonii are transferred to human stem cells. This is achieved via the rational design of a chimeric protein-polymer surfactant cell membrane binding construct, comprising the cardiac fibronectin (Fn) bi...

Background: Pig skin is a widely acknowledged surrogate for human skin for in vitro/ex vivo skin penetration studies with application for small molecules and nanosystems. We have investigated the influence of biological factors such as age and anatomical site on the penetration and distribution of nanoparticles (2.1 nm hydrophilic CdTe/CdS quantum...

Background: Lymph node (LN) positivity is a prognostic indicator in patients with colon cancer regardless of age, and age is an important parameter that impacts therapeutic recommendations. But little is known about the impact of age on LN positivity in patients with colon cancer. Methods: We analyzed 257,334 patients with colon cancer diagnosed fr...

Background/aims: The mechanisms by which permeation enhancers increase human skin permeation of caffeine and naproxen were assessed in vitro. Methods: Active compound solubility in the vehicles and in the stratum corneum (SC), active compound flux across epidermal membranes and uptake of active and vehicle components into the SC were measured. T...

Skin-targeting microscale medical devices are becoming popular for therapeutic delivery and diagnosis. We used cryo-SEM, fluorescence lifetime imaging microscopy (FLIM), autofluorescence imaging microscopy and inflammatory response to study the puncturing and recovery of human skin ex vivo and in vivo after discretised puncturing by a microneedle a...

Zinc pyrithione is ubiquitous in commercial products particularly anti‐dandruff shampoos. For the efficacy of zinc pyrithione therapeutic cleansers to be assessed accurately, the distribution of particles on the scalp needs to be visualized. Currently, no technique is available which provides the chemical specificity and sensitivity required. Here,...

This overview on skin delivery considers the evolution of the principles of percutaneous absorption and skin products from ancient times to today. Over the ages, it has been recognised that products may be applied to the skin for either local or systemic effects. Major changes have occurred in our understanding of the skin and the sophistication in...

Aim: We evaluated the effects of the incorporation of zinc oxide (ZnO) nanoparticles in a mesoporous matrix, aiming to improve the textural, structural and morphological properties and verify their safety so that they can be applied in sunscreen cosmetics. Materials and methods: ZnO nano-particles were incorporated into an ordered mesoporous sil...

This work describe analgesic prescribing in poly-medicated patients and factors associated with it

Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development of these devices is dependent on understanding the macro-molecular diffusion properties of skin. We hypo...