Natalie Trevaskis

Natalie Trevaskis
Monash University (Australia) · Monash Institute of Pharmaceutical Sciences

BPharm PhD

About

79
Publications
32,413
Reads
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5,259
Citations
Citations since 2016
47 Research Items
3839 Citations
20162017201820192020202120220200400600800
20162017201820192020202120220200400600800
20162017201820192020202120220200400600800
20162017201820192020202120220200400600800
Additional affiliations
January 2006 - present
Position
  • Research Associate
January 2005 - December 2013

Publications

Publications (79)
Article
Full-text available
Although various vaccines are now commercially available, they have not been able to stop the spread of COVID-19 infection completely. An excellent strategy to get safe, effective, and affordable COVID-19 treatments quickly is to repurpose drugs that are already approved for other diseases. The process of developing an accurate and standardized dru...
Article
Full-text available
Liposomes are sphere-shaped vesicles that can capture therapeutics either in the outer phospholipid bilayer or inner aqueous core. Liposomes, especially when surface-modified with functional materials, have been used to achieve many benefits in drug delivery, including improving drug solubility, oral bioavailability, pharmacokinetics, and delivery...
Article
Full-text available
The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given circa 7817 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially available ex vivo/3D airway and a...
Article
Full-text available
SARS-CoV-2 is the cause of the COVID-19 pandemic which has claimed more than 6.5 million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as th...
Article
Dietary lipids, highly lipophilic drugs, antigens and immune cells are transported from the intestine to the mesenteric lymph nodes (MLNs) via mesenteric lymphatic vessels. Recently our lab reported that the mesenteric lymphatic vessels become highly branched and leak lymph to the surrounding mesenteric adipose tissue (MAT) in mice and humans with...
Preprint
Full-text available
Although various vaccines are now commercially available, they have not been able to stop the spread of COVID-19 infection completely. An excellent strategy to quickly get safe, effective, and affordable COVID-19 treatment is to repurpose drugs that are already approved for other diseases as adjuvants along with the ongoing vaccine regime. The proc...
Preprint
Full-text available
The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given the approximately 8,000 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially-available ex vivo/3D...
Preprint
Full-text available
SARS-CoV-2, is the cause of the COVID-19 pandemic which has claimed more than six million lives worldwide, devastating the economy and overwhelming healthcare systems globally. The development of new drug molecules and vaccines has played a critical role in managing the pandemic; however, new variants of concern still pose a significant threat as t...
Article
Recent reports have highlighted the role of the lymphatic system and its resident immune cells in the development of inflammatory arthritis. Directing therapeutics to the joint-draining lymphatics could improve access to lymphatic-resident pro-inflammatory immune cells, improve local treatment efficacy and enable the administration of lower drug do...
Article
Challenges to effective delivery of drugs following oral administration has attracted growing interest over recent decades. Small molecule drugs (<1000 Da) are generally absorbed across the gastrointestinal tract into the portal blood and further transported to the systemic circulation via the liver. This can result in a significant reduction to th...
Article
Vaccines are a powerful health intervention but there is still an unmet need for effective preventative and therapeutic vaccines for many diseases such as cancer and infections. Interstitial (e.g. subcutaneous (SC)) injection in nano-sized carriers such as high density lipoproteins (HDLs) can improve the access of vaccine subunit antigens or adjuva...
Article
The importance of kidney-gut crosstalk in driving kidney disease complications is increasingly being realized. However, little attention has been given to intestinal lymphatic changes in kidney disease. Zhong et al. report striking changes to intestinal lymphatic composition, structure, and function in proteinuric kidney injury models, including in...
Article
Full-text available
Lipophilic conjugates (LCs) of small molecule drugs have been used widely in clinical and pre-clinical studies to achieve a number of pharmacokinetic and therapeutic benefits. For example, lipophilic derivatives of drugs are employed in several long acting injectable products to provide sustained drug exposure for hormone replacement therapy and to...
Article
Full-text available
Visceral adipose tissue (VAT) encases mesenteric lymphatic vessels and lymph nodes through which lymph is transported from the intestine and mesentery. Whether mesenteric lymphatics contribute to adipose tissue inflammation and metabolism and insulin resistance is unclear. Here we show that obesity is associated with profound and progressive dysfun...
Article
Background The lymphatic system and the cardiovascular system work together to maintain body fluid homeostasis. Despite that, the lymphatic system has been relatively neglected as a potential drug target and a source of adverse effects from cardiovascular drugs. Like the heart, the lymphatic vessels undergo phasic contractions to promote lymph flow...
Article
Full-text available
Vaccination represents the best line of defense against infectious diseases and is crucial in curtailing pandemic spread of emerging pathogens to which a population has limited immunity. In recent years, mRNA vaccines have been proposed as the new frontier in vaccination, owing to their facile and rapid development while providing a safer alternati...
Article
The pulmonary lymphatic system comprises a vast network of lymph vessels and lymph nodes that unite the interstitial space with the vascular system, serving an essential role in fluid balance and immune response. Although ubiquitous in the lung parenchyma and mandatory for normal physiology, pulmonary lymph vessels are often not considered when des...
Article
Full-text available
A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-2251-7
Article
Full-text available
The absorption of oral drugs is frequently plagued by significant variability with potentially serious therapeutic consequences. The source of variability can be traced back to interindividual variability in physiology, differences in special populations (age- and disease-dependent), drug and formulation properties, or food-drug interactions. Clini...
Article
Full-text available
The mesenteric lymph nodes (MLN) are a key site for the generation of adaptive immune responses to gut-derived antigenic material and immune cells within the MLN contribute to the pathophysiology of a range of conditions including inflammatory and autoimmune diseases, viral infections, graft versus host disease and cancer. Targeting immunomodulatin...
Article
Orlistat is a pancreatic lipase (PL) inhibitor that inhibits dietary lipid absorption and is used to treat obesity. The oral bioavailability of orlistat is considered zero after administration in standard formulations. This is advantageous in the treatment of obesity. However, if orlistat absorption could be improved it has the potential to treat d...
Article
The advent of immunotherapy has revolutionised the treatment of some cancers. Harnessing the immune system to improve tumour cell killing is now standard clinical practice and immunotherapy is the first line of defence for many cancers that historically, were difficult to treat. A unifying concept in cancer immunotherapy is the activation of the im...
Article
Drug delivery to the lymphatic system is gaining increasing attention, particularly in fields such as immunotherapy where drug access to lymphocytes is central to activity. We have previously described a prodrug strategy that facilitates the lymphatic delivery of a model immunomodulator, mycophenolic acid (MPA) via incorporation into intestinal tri...
Article
The lymphatic system plays an integral role in the development and progression of a range of disease conditions, which has impelled medical researchers and clinicians to design, develop and utilize advanced lymphatic drug delivery systems. Following interstitial administration, most therapeutics and molecules are cleared from tissues via the draini...
Article
Interstitial administration (e.g. subcutaneous (SC) administration) of immunotherapies and vaccines within nanoparticles can improve access to lymph-resident immune cells leading to enhanced efficacy and reduced off-target effects. Recently, endogenous high-density lipoproteins (HDLs) were found to return from peripheral tissue back to the systemic...
Article
Increased delivery to immune cells in the cortex and paracortex of the lymph node can be achieved by conjugating cargo to nanoparticles via linkers that release at programmable rates.
Article
Full-text available
The intestinal lymphatic system transports fluid, immune cells, dietary lipids, and highly lipophilic drugs from the intestine to the systemic circulation. These transport functions are important to health and when dysregulated contribute to pathology. This has generated significant interest in approaches to deliver drugs to the lymphatics. Most of...
Article
Full-text available
Adipose tissue is an energy store and a dynamic endocrine organ1,2. In particular, visceral adipose tissue (VAT) is critical for the regulation of systemic metabolism3,4. Impaired VAT function—for example, in obesity—is associated with insulin resistance and type 2 diabetes5,6. Regulatory T (Treg) cells that express the transcription factor FOXP3 a...
Article
Recently peripheral lymphatic vessels were found to transport HDL from interstitial tissues to the blood circulation during reverse cholesterol transport. This function is critical to the clearance of cholesterol from atherosclerotic plaques. The role of organ-specific lymphatics in modulating HDL transport and composition is, however, incompletely...
Article
Drugs are commonly administered via the intraperitoneal (IP) route to treat localised infections and cancers in patients, and to test drug efficacy and toxicity in pre-clinical studies. Despite this, there remain large gaps in our understanding of drug absorption routes (lymph vs. blood) and pharmacokinetics following IP administration. This is par...
Article
Full-text available
The simultaneous intake of food and drugs can have a strong impact on drug release, absorption, distribution, metabolism and/or elimination and consequently, on the efficacy and safety of pharmacotherapy. As such, food-drug interactions are one of the main challenges in oral drug administration. Whereas pharmacokinetic (PK) food-drug interactions c...
Article
Lymphocytes play a central role in the pathology of a range of chronic conditions such as autoimmune disease, transplant rejection, leukemia, lymphoma HIV/AIDs and cardiometabolic diseases such as atherosclerosis. Current treatments for lymphocyte-associated conditions are incompletely effective and/or complicated by a range of off-target toxicitie...
Article
Therapeutic proteins can facilitate the targeting and treatment of lymphatic diseases (such as cancer metastases, infections and inflammatory diseases) since they are cleared via the lymphatics following interstitial (SC or IM) administration. However, therapeutic proteins are often administered intravenously (IV). Recently therapeutic proteins hav...
Article
Lipid based formulations (LBF) are a promising formulation strategy for many poorly water soluble drugs and have been shown previously to enhance the oral exposure of CP-532,623, an oral cholesteryl ester transfer protein inhibitor. In the current study, an in vitro lipid digestion model was used to probe the relationship between drug solubilisatio...
Article
The current studies sought to explore the impact of drug supersaturation and precipitation during the dispersion and digestion of lipid-based formulations (LBF), on in vivo absorption using a coupled in vitro digestion - in vivo perfusion absorption model. Fenofibrate absorption was evaluated from a number of LBFs with different solubilisation and...
Article
Prodrugs In their Communication on page 13700 ff., J. S. Simpson, C. H. J. Porter et al. report how the oral bioavailability of testosterone is significantly enhanced by generating glyceride-based prodrugs that promote drug release and direct the drugs to the lymphatic system.
Article
Propharmaka In der Zuschrift auf S. 13904 ff. demonstrieren J. S. Simpson, C. J. H. Porter et al. eine Verbesserung der oralen Bioverfügbarkeit von Testosteron durch Synthese Glycerid-basierter Propharmaka, die die Wirkstoff-Freisetzung fördern und die Wirkstoffe zum lymphatischen System leiten.
Article
Vesicular and colloidal delivery systems can be designed to control drug release spatially and temporally to improve drug efficacy and side effect profiles. Niosomes (vesicles prepared from nonionic surfactants in aqueous media) are gaining interest as an alternative vesicular delivery system as they offer advantages such as biocompatibility, chemi...
Article
In previous studies, a triglyceride (TG) mimetic prodrug of the model immunomodulator mycophenolic acid (MPA), was shown to significantly enhance lymphatic transport of MPA-related species in the rat. The rat gastrointestinal tract, however, is somewhat different to that in higher order species such as dogs and humans and may underestimate lymphati...
Article
First-pass hepatic metabolism can significantly limit oral drug bioavailability. Drug transport from the intestine through the lymphatic system, rather than the portal vein, circumvents first-pass metabolism. However, the majority of drugs do not have the requisite physicochemical properties to facilitate lymphatic access. Herein, we describe a pro...
Article
First-pass hepatic metabolism can significantly limit oral drug bioavailability. Drug transport from the intestine through the lymphatic system, rather than the portal vein, circumvents first-pass metabolism. However, the majority of drugs do not have the requisite physicochemical properties to facilitate lymphatic access. Herein, we describe a pro...
Article
Full-text available
Purpose: In vitro lipid digestion models are commonly used to screen lipid-based formulations (LBF), but in vitro-in vivo correlations are in some cases unsuccessful. Here we enhance the scope of the lipid digestion test by incorporating an absorption 'sink' into the experimental model. Methods: An in vitro model of lipid digestion was coupled d...
Article
Lipid based formulations (LBF) provide well proven opportunities to enhance the oral absorption of drugs and drug candidates that sit close to, or beyond, the boundaries of Lipinski's 'rule-of-five' chemical space. Advantages in permeability, efflux and pre-systemic metabolism are evident; however, the primary benefit is in increases in dissolution...
Article
The triglyceride (TG) mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) biochemically integrates into intestinal lipid transport and lipoprotein assembly pathways and thereby promotes the delivery of mycophenolic acid (MPA) into the lymphatic system. As lipoprotein (LP) formation occurs constitutively, even in the fasted state, t...
Article
The lymphatic system serves an integral role in fluid homeostasis, lipid metabolism and immune control. In cancer, the lymph nodes that drain solid tumours are a primary site of metastasis, and recent studies have suggested intrinsic links between lymphatic function, lipid deposition, obesity and atherosclerosis. Advances in the current understandi...
Article
Full-text available
The intestinal lymphatic system plays key roles in fluid transport, lipid absorption and immune function. Lymph flows directly from the small intestine via a series of lymphatic vessels and nodes that converge at the superior mesenteric lymph duct. Cannulation of the mesenteric lymph duct thus enables the collection of mesenteric lymph flowing from...
Article
The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-...
Article
Full-text available
Purpose: Recent studies have demonstrated the potential for a triglyceride (TG) mimetic prodrug to promote the delivery of mycophenolic acid (MPA) to the lymphatic system. Here, the metabolic pathways that facilitate the lymphatic transport of the TG prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) were examined to better inform the de...
Article
The present study investigated the use of lipid based drug delivery systems to enhance the oral bioavailability of the CETP inhibitors CP-532,623 and torcetrapib. A series of self-emulsifying lipid based drug delivery systems (SEDDS) were assembled and examined using an in vitro lipid digestion model to evaluate patterns of drug precipitation under...
Article
A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may...
Article
Full-text available
Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug...
Article
Full-text available
Drugs with low aqueous solubility commonly show low and erratic absorption after oral administration. Myriad approaches have therefore been developed to promote drug solubilization in the gastrointestinal (GI) fluids. Here, we offer insight into the unique manner by which lipid-based formulations (LBFs) may enhance the absorption of poorly water-so...
Article
This work investigates the influence of drug absorption route (intestinal lymphatics vs. blood supply) on drug pharmacokinetics and tissue distribution. To achieve this aim, the pharmacokinetics and tissue distribution of model compounds [1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane, DDT; halofantrine] and lipids were assessed following intravenou...
Article
Full-text available
To evaluate the potential for the acidic intestinal unstirred water layer (UWL) to induce drug supersaturation and enhance drug absorption from intestinal mixed micelles, via the promotion of fatty acid absorption. Using a single-pass rat jejunal perfusion model, the absorptive-flux of cinnarizine and (3)H-oleic acid from oleic acid-containing inte...
Article
Co-administration of poorly water-soluble drugs (PWSD) with dietary or formulation lipids stimulates the formation of lipid colloidal phases such as vesicular and micellar species, and significantly expands the drug solubilization capacity of the small intestine. The mechanism of drug absorption from the solubilizing phases, however, has not been f...
Article
The oral bioavailability of poorly water-soluble drugs (PWSD) is often significantly enhanced by co-administration with lipids in food or lipid based oral formulations. Co-administration with lipids promotes drug solubilization in intestinal mixed micelles and vesicles, however, the mechanism(s) by which PWSD are absorbed from these dispersed phase...
Article
Full-text available
Purpose: To establish a lymph-cannulated mouse model, and use the model to investigate the impact of lipid dose on exogenous and endogenous lipid recruitment, and drug transport, into the lymph of males versus females. Finally, lymphatic transport and drug absorption in the mouse were compared to other pre-clinical models (rats/dogs). Methods: A...
Article
The clearance (Cl) and volume of distribution (V(ss)) of a lipophilic, lymphatically transported drug, halofantrine (Hf) have been evaluated after intravenous delivery to the systemic circulation in ex vivo lymph and plasma, and compared with the data obtained after administration of a lipid-based emulsion and a lipid-free cosolvent formulation. Sy...
Article
The clearance (Cl) and volume of distribution (V ss) of a lipophilic, lymphatically transported drug, halofantrine (Hf) have been evaluated after intravenous delivery to the systemic circulation in ex vivo lymph and plasma, and compared with the data obtained after administration of a lipid‐based emulsion and a lipid‐free cosolvent formulation. Sys...
Article
Elevated systemic levels of triglyceride-rich lipoproteins (TRL) are a risk factor for the development of atherosclerosis. In patients with metabolic syndrome (MetS), intestinal TRL overproduction contributes to high systemic TRL levels, and recent studies suggest that systemic changes in MetS such as increases in plasma fatty acids and insulin res...