Mechanistic in vivo studies of secondary skin-to-skin peanut allergen transfer to determine the impact of hand washing in reducing the risk of cutaneous sensitization.

Background: In Europe, 1-2% of children are diagnosed with a peanut allergy. Atopic dermatitis (AD) is a significant risk factor for food allergy development, with cutaneous allergen exposure playing a causative role in allergic sensitization, particularly in early childhood.

Objectives: To investigate the primary and secondary skin-to-skin transfer of peanut proteins and the impact of hand washing in reducing allergen transfer.

A multistage double-blind placebo-controlled study to assess the safety and efficacy of transdermal vitamin D phosphate supplementation (TransVitD).

Background: Lifestyle changes have meant that it is problematic for many people across the globe to maintain adequate vitamin D concentrations. As UV-catalysed production in the skin, which uses vitamin D-binding protein to facilitate systemic absorption, is the primary source of vitamin D, it is questionable if oral supplementation of this vitamin is the optimal means to replace it. However, supplementing an oil-soluble vitamin via the skin is problematic as it gets stuck in the stratum corneum after topical application.

Professional Competencies and Capabilities in the Development of Medicines.

The medicines development workforce has grown to be a multidisciplinary, interprofessional global body of broadly qualified graduate professionals working with and around the biopharmaceutical industry. To satisfy their demands of fitness for work, they must meet the changes and challenges of a rapidly developing technological and competitive field. This has generated a need for a harmonised, mutually recognised vocational programme of competencies and capabilities, based on an academic foundation, which for the adult learners in medicines development goes above and beyond their original medical and scientific specialisms.

Ethnic Differences in Response to Oral Vitamin D Supplementation: A Systematic Review and Meta-analysis.

Context: Individual variability in oral vitamin D supplement response hinders the understanding of its clinical impact, and while ethnicity has been implicated in this variability it has not been well described.

Objective: The aim was to systematically assess the impact of ethnicity on response to oral vitamin D supplementation.

Data Source: The Web of Science and PubMed databases were searched for articles published from 1960 to the end of 2020.

Systematic review and QSPR analysis of chemical penetration through the nail to inform onychomycosis candidate selection.

Recalcitrant nail plate infections can be life-long problems because localizing antifungal agents into infected tissues is problematic. In this systematic review, guided by the SPIDER method, we extracted chemical nail permeation data for 38 compounds from 16 articles, and analyzed the data using quantitative structure-property relationships (QSPRs). Our analysis demonstrated that low-molecular weight was essential for effective nail penetration, with <120 g/mol being preferred.

Laser-cutting: A novel alternative approach for point-of-care manufacturing of bespoke tablets.

A novel subtractive manufacturing method to produce bespoke tablets with immediate and extended drug release is presented. This is the first report on applying fusion laser cutting to produce bespoke furosemide solid dosage forms based on pharmaceutical-grade polymeric carriers. Cylindric tablets of different sizes were produced by controlling the two-dimensional design of circles of the corresponding diameter.

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device.

Objectives: To develop a simulation model to explore the interplay between mechanical stretch and diffusion of large molecules into the skin under locally applied hypobaric pressure, a novel penetration enhancement method.

Methods: Finite element method was used to model the skin mechanical deformation and molecular diffusion processes, with validation against in-vitro transdermal permeation experiments. Simulations and experimental data were used together to investigate the transdermal permeation of large molecules under local hypobaric pressure.

Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.

Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia.

Investigating how amine structure influences drug-amine ion-pair formation and uptake via the polyamine transporter in A549 lung cells.

Transiently associating amines with therapeutic agents through the formation of ion-pairs has been established both in vitro and in vivo as an effective means to systemically direct drug delivery to the lung via the polyamine transport system (PTS). However, there remains a need to better understand the structural traits required for effective PTS uptake of drug ion-pairs. This study aimed to use a structurally related series of amine counterions to investigate how they influenced the stability of theophylline ion-pairs and their active uptake in A549 cells.

Nanomaterials fusing with the skin: Alpha-tocopherol phosphate delivery into the viable epidermis to protect against ultraviolet radiation damage.

Vitamin E (alpha tocopherol, α-T) is an important skin antioxidant, but its penetration into the viable epidermis, where it acts, is very limited. This study investigated if phosphorylating α-tocopherol (α-TP) to form a provitamin, improved its interactions with skin, its passage into the tissue, and thus its ability to protect the skin from ultraviolet radiation (UVR) damage. At pH 7.

A Cyclodextrin-Stabilized Spermine-Tagged Drug Triplex that Targets Theophylline to the Lungs Selectively in Respiratory Emergency.

Ion-pairing a lifesaving drug such as theophylline with a targeting moiety could have a significant impact on medical emergencies such as status asthmaticus or COVID-19 induced pneumomediastinum. However, to achieve rapid drug targeting in vivo the ion-pair must be protected against breakdown before the entry into the target tissue. This study aims to investigate if inserting theophylline, when ion-paired to the polyamine transporter substrate spermine, into a cyclodextrin (CD), to form a triplex, could direct the bronchodilator to the lungs selectively after intravenous administration.

Quality and use of unlicensed vitamin D preparations in primary care in England: Retrospective review of national prescription data and laboratory analysis.

Aim: To evaluate the type (licensed vs unlicensed) and cost of preparations used to fulfil vitamin D prescriptions in England over time, and to compare measured vitamin D content of selected vitamin D preparations against labelled claim.

Methods: Retrospective analysis of vitamin D prescription data in primary care in England (2008-2018). Laboratory analysis of 13 selected vitamin D preparations.

Using Polar Ion-Pairs to Control Drug Delivery to the Airways of the Lungs.

The rapid absorptive clearance of drugs delivered to the airways of the lungs means that many inhaled medicines have a short duration of action. The aim of this study was to investigate whether forming polar ion-pairs can modify drug absorption to slow down clearance from the airways. Salbutamol was used as a model drug and was formulated as ion-pairs in an aqueous solution with three negatively charged hydrophilic counterions: sulfate (molecular weight (MW) 142), gluconate (MW 218), and phytate (MW 736) (association constants of 1.

Targeting macrophages and their recruitment in the oral cavity using swellable (+) alpha tocopheryl phosphate nanostructures.

The phosphorylation of (+) alpha tocopherol produces adhesive nanostructures that interact with oral biofilms to restrict their growth. The aim of this work was to understand if these adhesive (+) alpha tocopheryl phosphate (α-TP) nanostructures could also control macrophage responses to the presence of oral bacteria. The (+) α-TP planar bilayer fragments (175 nm ± 21 nm) formed in a Trizma®/ethanol vehicle swelled when exposed to the cell lines (maximum stabilized size = 29 μm).

Mucus penetrating properties of soft, distensible lipid nanocapsules.

Designing nanomaterials to release their drug pay-load upon exposure to an exogenous trigger can help to direct drug delivery, but how the triggered release, which often modifies the nanomaterial properties, influences the biological fate of these systems is currently unknown. The aim of this study was to investigate how the triggered drug release from PEG coated, soft, 50 nm distensible lipid nanocapsules (LNC) influenced their diffusion across a mucus barrier. The translocation speed of the non-triggered LNC across a 35 µm thick purified gastric mucin (PGM) barrier was 3 times faster (30.

Diminishing biofilm resistance to antimicrobial nanomaterials through electrolyte screening of electrostatic interactions.

The extracellular polymer substances (EPS) generated by biofilms confers resistance to antimicrobial agents through electrostatic and steric interactions that hinder molecular diffusion. This resistance mechanism is particularly evident for antibacterial nanomaterials, which inherently diffuse more slowly compared to small organic antibacterial agents. The aim of this study was to determine if a biofilm's resistance to antibacterial nanomaterial diffusion could be diminished using electrolytes to screen the EPS's electrostatic interactions.

Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung.

Introduction: Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy.

Soft, adhesive (+) alpha tocopherol phosphate planar bilayers that control oral biofilm growth through a substantive antimicrobial effect.

'Soft' nanomaterials have the potential to produce substantive antibiofilm effects. The aim of this study was to understand the oral antimicrobial activity of soft nanomaterials generated from alpha-tocopherol (α-T) and alpha-tocopherol phosphate (α-TP). (+) α-TP formed planar bilayer islands (175 ± 21 nm, -14.

Ion-Pairing with Spermine Targets Theophylline To the Lungs via the Polyamine Transport System.

Certain xenobiotics, such as paraquat, are sequestered into the lungs from the systemic circulation by the polyamine transporter system (PTS). The aim of this study was to investigate whether ion-pairing a drug (theophylline) with a PTS substrate (spermine) provides a means of using this active transport mechanism to target drug delivery to the lungs. Fourier transform infrared spectroscopy showed that two of the amine groups of spermine interact with C-N and C═O of theophylline, leaving two free amines to interact with the PTS.

The value of virtual conferencing for ecology and conservation.

The objectives of conservation science and dissemination of its research create a paradox: Conservation is about preserving the environment, yet scientists spread this message at conferences with heavy carbon footprints. Ecology and conservation science depend on global knowledge exchange-getting the best science to the places it is most needed. However, conference attendance from developed countries typically outweighs that from developing countries that are biodiversity and conservation hotspots.

Using Salt Counterions to Modify β-Agonist Behavior in Vivo.

There is a paucity of data describing the impact of salt counterions on the biological performance of inhaled medicines in vivo. The aim of this study was to determine if the coadministration of salt counterions influenced the tissue permeability and airway smooth muscle relaxation potential of salbutamol, formoterol, and salmeterol. The results demonstrated that only salbutamol, when formulated with an excess of the 1-hydroxy-2-naphthoate (1H2NA) counterion, exhibited a superior bronchodilator effect (p < 0.

New insights into eutectic cream skin penetration enhancement.

The manner in which the eutectic cream EMLA enhances the percutaneous penetration of lidocaine and prilocaine into human skin is still not fully understood. The purpose of this study was to investigate if the modification of drug aggregation played a role in the way EMLA facilitates delivery. Light scattering analysis of lidocaine alone in water gave a critical aggregation concentration (CAC) of 572 μM and a mean aggregate size of 58.

Triggered-release nanocapsules for drug delivery to the lungs.

This study demonstrated the feasibility of trigger-responsive inhaled delivery of medicines using soft solid shelled nanocapsules. The delivery system was a 50nm sized lipid rich capsule carrier that distended rapidly when mixed with an exogenous non-ionic surfactant trigger, Pluronic® L62D. Capsule distension was accompanied by solid shell permeabilisation which resulted in payload release from the carrier; 63.

Quantitative assessment of nanoparticle surface hydrophobicity and its influence on pulmonary biocompatibility.

To date, the role of nanoparticle surface hydrophobicity has not been investigated quantitatively in relation to pulmonary biocompatibility. A panel of nanoparticles spanning three different biomaterial types, pegylated lipid nanocapsules, polyvinyl acetate (PVAc) and polystyrene nanoparticles, were characterized for size, surface charge, and stability in biofluids. Surface hydrophobicity of five nanoparticles (50-150nm) was quantified using hydrophobic interaction chromatography (HIC) and classified using a purpose-developed hydrophobicity scale: the HIC index, range from 0.