Metabolic glycan labelling with bio-orthogonal targeting and its potential in drug delivery.

New modes of targeted drug delivery are emerging with promise of enhancing therapeutic efficacy while reducing side effects. This review examines the landscape of metabolic glycan labelling-a technique gaining traction for its potential in specific drug targeting. By exploiting the natural glycan synthetic pathway of monosaccharides, unnatural sugar analogues are incorporated into glycoproteins, allowing for the presentation of unique functional groups on cells.

Human milk improves the oral bioavailability of the poorly water-soluble drug clofazimine.

Clofazimine is an emerging drug for the treatment of cryptosporidiosis in infants. As a poorly water-soluble drug, the formulation of clofazimine in age-appropriate vehicles is challenging and often results in the use of off-label formulations. Milk-based vehicles such as human milk and bovine milk have been investigated as age-appropriate formulations and shown to increase the solubilisation of poorly water-soluble drugs via enhanced solubility in lipid digestion products in vitro.

Montmorillonite restricts free fatty acid liberation and alters self-assembled structures formed during in vitro lipid digestion.

The global rise in obesity necessitates innovative weight loss strategies. Naturally occurring smectite clays, such as montmorillonite (MMT), offer promise due to their unique properties that interfere with free fatty acid (FFA) liberation, reducing systemic uptake. However, the mechanisms of MMT-FFA interactions and their implications for weight management are undefined.

Dietary resistant starch enhances immune health of the kidney in diabetes via promoting microbially-derived metabolites and dampening neutrophil recruitment.

Background: Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and immunomodulatory effects have not yet been fully elucidated.

Methods: Six-week-old db/db mice were fed a diet containing 12.

Compartmentalised enzyme-induced phase transformations in self-assembling lipid systems.

Hypothesis: Understanding the digestion of lipid-based pharmaceutical formulations and food systems is necessary for optimising drug and nutrient delivery and has been extensively studied in bulk emulsion systems using the pH-stat method [1]. However, this approach is not suitable for investigation of individual lipid droplets, in particular the interface where the lipase acts. Microfluidic approaches to study digestion at lipid-water interfaces using droplet trapping have been proposed, however the aqueous phase in that case washes over the interface presenting uncertainty over the stoichiometry of interactions [2].

Infant formula as a solid lipid dose form for enhancement of the oral bioavailability of cannabidiol for paediatric patients.

Cannabinoids can save paediatric patients from harmful psychological conditions caused by epilepsy. However, the limited aqueous solubility of the drug presents a limitation to oral absorption and bioavailability. Previous studies have shown the enhancement of oral bioavailability for poorly water-soluble drugs using milk or milk-based products like infant formula as a novel lipid-based formulation, due to digestion of the lipids to enhance drug solubility that is particularly well suited to infants and in low economy settings.

The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury.

Acute kidney injury (AKI) disrupts energy metabolism. Targeting metabolism through AMP-activated protein kinase (AMPK) may alleviate AKI. ATX-304, a pan-AMPK activator, was evaluated in C57Bl/6 mice and tubular epithelial cell (TEC) cultures.

Precision peptide theranostics: developing - to -terminus optimized theranostics targeting cholecystokinin-2 receptor.

Peptides are ideal for theranostic development as they afford rapid target accumulation, fast clearance from background tissue, and exhibit good tissue penetration. Previously, we developed a novel series of peptides that presented discreet folding propensity leading to an optimal candidate [Ga]Ga-DOTA- ([D-Glu]-Ala-Tyr-MeGly-Trp-MeNle-Asp-Nal-NH) with 50 pM binding affinity against cholecystokinin-2 receptors (CCKR). However, we were confronted with challenges of unfavorably high renal uptake.

Hit-to-lead optimization of 2-aminoquinazolines as anti-microbial agents against Leishmania donovani.

Visceral leishmaniasis is a potentially fatal disease caused by infection by the intracellular protist pathogens Leishmania donovani or Leishmania infantum. Present therapies are ineffective because of high costs, variable efficacy against different species, the requirement for hospitalization, toxicity and drug resistance. Detailed analysis of previously published hit molecules suggested a crucial role of 'guanidine' linkage for their efficacy against L.

Caffeine consumed prior to cardiac stress testing may affect diagnostic accuracy of nuclear medicine myocardial imaging of myocardial ischemia: A systematic review and meta-analysis.

Background: Myocardial perfusion imaging (MPI) is a well-established, non-invasive imaging procedure for the diagnosis and evaluation of patients with known or suspected coronary artery disease. With the increasing use of pharmacologic stress agents in myocardial perfusion imaging, strict preparation, including caffeine abstinence, is required. The aim of this review was to determine the effect of caffeine consumed prior to nuclear cardiac stress testing on the diagnostic accuracy.

Trajectories of oral bisphosphonate use after hip fractures: a population-based cohort study.

Unlabelled: Bisphosphonates prevent future hip fractures. However, we found that one in six patients with hip fractures had a delay in bisphosphonate initiation and another one-sixth discontinued treatment within 12 months after discharge. Our results highlight the need to address hesitancy in treatment initiation and continuous monitoring.

Liposomal formulation of a new antifungal hybrid compound provides protection against in the skin colonization model.

The newly emerged pathogen, , presents a serious threat to public health worldwide. This multidrug-resistant yeast often colonizes and persists on the skin of patients, can easily spread from person to person, and can cause life-threatening systemic infections. New antifungal therapies are therefore urgently needed to limit and control both superficial and systemic infections.

Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products-induced inflammation.

Glucagon like peptide-1 (GLP-1) is a hormone produced and released by cells of the gastrointestinal tract following meal ingestion. GLP-1 receptor agonists (GLP-1RA) exhibit kidney-protective actions through poorly understood mechanisms. Here we interrogated whether the receptor for advanced glycation end products (RAGE) plays a role in mediating the actions of GLP-1 on inflammation and diabetic kidney disease.

Distinguishing Inducible and Non-Inducible Resistance to Colistin in Pseudomonas aeruginosa by Quantitative and Systems Pharmacology Modeling at Low and Standard Inocula.

Colistin is a polymyxin and peptide antibiotic that can yield rapid bacterial killing, but also leads to resistance emergence. We aimed to develop a novel experimental and Quantitative and Systems Pharmacology approach to distinguish between inducible and non-inducible resistance. Viable count profiles for the total and less susceptible populations of Pseudomonas aeruginosa ATCC 27853 from static and dynamic in vitro infection models were simultaneously modeled.

Evaluating human milk as a drug delivery vehicle for clofazimine to premature infants.

Human milk is proposed as a drug delivery vehicle suitable for use in neonatal patients. Clofazimine, traditionally used for the treatment of leprosy and tuberculosis, is emerging as a treatment for cryptosporidiosis in infants, however its poor aqueous solubility has led to its commercial formulation as a waxy lipid formulation in a capsule, a format that is not suitable for infants. In this study, the evaluation of pasteurised human milk for the delivery of clofazimine was investigated using an in vitro lipolysis model to simulate gastric and intestinal digestion.

In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy.

Low-frequency Raman spectroscopy (LFRS) is a valuable tool to detect the solid state of amorphous and crystalline drugs in solid dosage forms and the transformation of drugs between different polymorphic forms. It has also been applied to track the solubilisation of solid drugs as suspensions in milk and infant formula during in vitro digestion. This study reports the use of LFRS as an approach to probe drug precipitation from a lipid-based drug delivery system (medium-chain self-nanoemulsifying drug delivery system, MC-SNEDDS) during in vitro digestion.

Development of Highly Potent Clinical Candidates for Theranostic Applications against Cholecystokinin-2 Receptor Positive Cancers.

Peptide receptor radionuclide therapy (PRRT) is a promising form of systemic radiation therapy designed to eradicate cancer. Cholecystokinin-2 receptor (CCKR) is an important molecular target that is highly expressed in a range of cancers. This study describes the synthesis and characterization of a novel series of Lu-labeled peptides ([Lu]Lu--) in comparison with the reference CCKR-targeting peptide CP04 ([Lu]Lu-).

Delivery and Expression of mRNA in the Secondary Lymphoid Organs Drive Immune Responses to Lipid Nanoparticle-mRNA Vaccines after Intramuscular Injection.

Lipid nanoparticles (LNPs) are the prime delivery vehicle for mRNA vaccines. Previous hypotheses suggested that LNPs contribute to innate reactogenicity and lead to the establishment of a vaccine adaptive response. It has not been clear whether LNP adjuvancy in the muscle is the prime driver of adaptive immune responses or whether delivery to secondary lymphatic organs is necessary to induce strong adaptive responses.

Survey content validation evaluating the dissemination and implementation of deprescribing guidelines.

Background: Policies, protocols and processes within organisations can facilitate or hinder guideline adoption. There is limited knowledge on the strategies used by organisations to disseminate and implement evidence-based deprescribing guidelines or their impact.

Methods: We aimed to develop an online survey targeting key organisations involved in deprescribing guideline endorsement, dissemination, modification or translation internationally.

Drug Discovery and Development Targeting Dementia.

Dementia, most often associated with neurodegenerative diseases, affects millions of people worldwide, predominantly the elderly. Unfortunately, no treatment is still available. Therefore, there is an urgent need to address this situation.

Hip fracture incidence and post-fracture mortality in Victoria, Australia: a state-wide cohort study.

Unlabelled: Hip fractures are a major public health concern. Number of hip fractures cases increased by 20% from 2012 to 2018. Factors associated with post-fracture mortality included men, those who are frail, living in a non-metropolitan region, or residing in a residential aged care facility.

Diagnostic Performance of Different Laboratory Methods for the Detection of Extrapulmonary Tuberculosis.

Accurate and appropriate extrapulmonary tuberculosis (EPTB) diagnosis remains challenging due to its paucibacillary nature, requirement of invasive collection procedures, and lack of sensitive tests. This study investigated the diagnostic performance of different methods for the diagnosis of EPTB. A total of 1340 EPTB specimens were collected from presumptive EPTB patients from four different hospitals between November 2015 and March 2017.

Mesoporous Silica Nanoparticles as a Potential Nanoplatform: Therapeutic Applications and Considerations.

With advances in nanotechnology, nanoparticles have come to be regarded as carriers of therapeutic agents and have been widely studied to overcome various diseases in the biomedical field. Among these particles, mesoporous silica nanoparticles (MSNs) have been investigated as potential nanocarriers to deliver drug molecules to various target sites in the body. This review introduces the physicochemical properties of MSNs and synthesis procedures of MSN-based nanoplatforms.

A novel droplet-based approach to study phase transformations in lyotropic liquid crystalline systems.

Hypothesis: Lyotropic liquid crystals (LLC) and their phase transformations in response to stimuli have gathered much interest for controlled and 'on-demand' drug applications. Bulk methods of preparation impose limitations on studying the transformations, especially induced by compositional changes, such as enzymatic changes to lipid structure. Here we hypothesise that controlled microfluidic production and coalescence of dissimilar aqueous and lipid droplets emulsified in a third mutually immiscible liquid will provide a new approach to the spatio-temporal study of structure formation in lyotropic liquid crystalline materials.