A peptide-based hydrogel sequence was computationally predicted from the Ala-rich cross-linked domains of elastin. Three candidate peptides were subsequently synthesised and characterised as potential drug delivery vehicles. The elastin-derived peptides are Fmoc-FFAAAAKAA-NH, Fmoc-FFAAAKAA-NH, and Fmoc-FFAAAKAAA-NH.
View Article and Find Full Text PDFThe interaction between genipin and a model protein bovine serum albumin (BSA), with and without the addition of acetic acid, has been studied experimentally and by modelling. The number of amino groups available to react was determined to be 5.6 % of the total number of amino acid building blocks on BSA.
View Article and Find Full Text PDFWe report a simple and reproducible micromoulding technique that dynamically fills microneedle moulds with a liquid formulation, using a plastic syringe, triggered by the application of vacuum ('vac-and-fill'). As pressure around the syringe drops, air inside the syringe pushes the plunger to uncover an opening in the syringe and fill the microneedle mould without manual intervention, therefore removing inter-operator variability. The technique was validated by monitoring the plunger movement and pressure at which the mould would be filled over 10 vacuum cycles for various liquid formulation of varying viscosity (water, glycerol, 20 % polyvinylpyrrolidone (PVP) solution or 40 % PVP solution).
View Article and Find Full Text PDFRecent infectious disease outbreaks, such as COVID-19 and Ebola, have highlighted the need for rapid and accurate diagnosis to initiate treatment and curb transmission. Successful diagnostic strategies critically depend on the efficiency of biological sampling and timely analysis. However, current diagnostic techniques are invasive/intrusive and present a severe bottleneck by requiring specialist equipment and trained personnel.
View Article and Find Full Text PDFTransmucosal drug delivery includes the administration of drugs via various mucous membranes, such as gastrointestinal, nasal, ocular, and vaginal mucosa. The use of nanoparticles in transmucosal drug delivery has several advantages, including the protection of drugs against the harsh environment of the mucosal lumens and surfaces, increased drug residence time, and enhanced drug absorption. Due to their relatively simple synthetic methods for preparation, safety profile, and possibilities of surface functionalisation, silica nanoparticles are highly promising for transmucosal drug delivery.
View Article and Find Full Text PDFMinimally invasive, reliable and low-cost in vivo biosensors that enable real-time detection and monitoring of clinically relevant molecules and biomarkers can significantly improve patient health care. Microneedle array (MNA)-based electrochemical sensors offer exciting prospects in this respect, as they can sample directly from the skin. However, their acceptability is dependent on developing a highly scalable and cost-effective fabrication strategy.
View Article and Find Full Text PDFIn this study, we synthesised thiolated silica nanoparticles using 3-mercaptopropyltrimethoxysilane and functionalised them with either 5 kDa methoxy polyethylene glycol maleimide (PEG) or 5 kDa alkyne-terminated poly(2-ethyl-2-oxazoline) (POZ). The main objectives of this study are to investigate the effects of pH on the size and ξ-potential of these nanoparticles and evaluate their mucoadhesive properties ex vivo using rat intestinal mucosa. The sizes of thiolated, PEGylated and POZylated silica nanoparticles were 53 ± 1, 68 ± 1 and 59 ± 1 nm, respectively.
View Article and Find Full Text PDFBiofilm formation in wounds is considered a major barrier to successful treatment, and has been associated with the transition of wounds to a chronic non-healing state. Here, we present a novel laboratory model of wound biofilm formation using porcine skin and a custom burn wound array device. The model supports high-throughput studies of biofilm formation and is compatible with a range of established methods for monitoring bacterial growth, biofilm formation, and gene expression.
View Article and Find Full Text PDFThis special issue, which is entitled “Penetration Enhancement of Topical Formulations”, presents a selection of the latest research that elucidates the challenges facing topical formulations for human skin in addition to proposing interesting solutions.[…].
View Article and Find Full Text PDFImmunodiagnostic microneedles provide a novel way to extract protein biomarkers from the skin in a minimally invasive manner for analysis in vitro. The technology could overcome challenges in biomarker analysis specifically in solid tissue, which currently often involves invasive biopsies. This study describes the development of a multiplex immunodiagnostic device incorporating mechanisms to detect multiple antigens simultaneously, as well as internal assay controls for result validation.
View Article and Find Full Text PDFPorcine ear skin is widely used to study skin permeation and absorption of ester compounds, whose permeation and absorption profiles may be directly influenced by in situ skin esterase activity. Importantly, esterase distribution and activity in porcine ear skin following common protocols of skin handling and storage have not been characterised. Thus, we have compared the distribution and hydrolytic activity of esterases in freshly excised, frozen, heated and explanted porcine ear skin.
View Article and Find Full Text PDFA novel topical codrug, naproxyl-dithranol (Nap-DTH), in which dithranol and naproxen are linked via an ester in a 1:1 ratio to form a single chemical entity, was synthesized. The antiproliferative, anti-inflammatory and toxic effects of Nap-DTH were assessed, at the cellular level, using various in vitro methods. Cultured HaCaT keratinocytes were treated with Nap-DTH, and the cellular effects were compared with those of the parent compounds, individually and as a 1:1 mixture of naproxen:dithranol to mimic 1:1 in situ liberation from Nap-DTH.
View Article and Find Full Text PDFAm J Respir Crit Care Med
December 2011
Rationale: Children with congenital heart disease are at risk of gut barrier dysfunction and translocation of gut bacterial antigens into the bloodstream. This may contribute to inflammatory activation and organ dysfunction postoperatively.
Objectives: To investigate the role of intestinal injury and endotoxemia in the pathogenesis of organ dysfunction after surgery for congenital heart disease.
The presence of resident Langerhans cells (LCs) in the epidermis makes the skin an attractive target for DNA vaccination. However, reliable animal models for cutaneous vaccination studies are limited. We demonstrate an ex vivo human skin model for cutaneous DNA vaccination which can potentially bridge the gap between pre-clinical in vivo animal models and clinical studies.
View Article and Find Full Text PDFSmall interfering RNA (siRNA), antisense oligonucleotides (ODNs), ribozymes and DNAzymes have emerged as sequence-specific inhibitors of gene expression that may have therapeutic potential in the treatment of a wide range of diseases. Due to their rapid degradation in vivo, the efficacy of naked gene silencing nucleic acids is relatively short lived. The entrapment of these nucleic acids within biodegradable sustained-release delivery systems may improve their stability and reduce the doses required for efficacy.
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