The influence of amphiphilic quaternary ammonium palmitoyl glycol chitosan (GCPQ) polymer composition on oil-loaded nanocapsule architecture.

Hypothesis: Predicting the exact nature of the self-assembly of amphiphilic molecules into supramolecular structures is of utmost importance for a variety of applications, but this is a challenge for nanotechnology. The amphiphilic drug delivery polymer-N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) self-assembles in aqueous media to form nanoparticles.

Experiment: This work aimed to develop a systematic predictive mathematical model on the eventual nature of oil-loaded GCPQ-nanoparticles and to determine the main independent variables that affect their nanoarchitecture following self-assembly.

A one-step method for generating antimicrobial nanofibre meshes coaxial electrospinning.

Respiratory diseases, including influenza, infectious pneumonia, and severe acute respiratory syndrome (SARS), are a leading cause of morbidity and mortality worldwide. The recent COVID-19 pandemic claimed over 6.9 million lives globally.

Targeting Intracranial Tumours with a Combination of RNA and Chemotherapy.

Glioblastoma multiforme (GBM) is a fast-growing and aggressive brain tumour, which remains largely resistant to treatment; the prognosis for patients is poor, with a median survival time of about 12-18 months, post diagnosis. In an effort to bring more efficacious treatments to patients, we targeted the down regulation of ITCH, an E3 ligase that is overexpressed in a variety of cancers, and which inhibits P73, a tumour suppressor gene. 6-O-glycolchitosan (GC) was used to deliver siRNA ITCH (GC60-siRNA-ITCH) and gemcitabine via the nose to brain route in CD-1 nude mice which had previously been implanted intracranially with U87-MG-luc2 cells.

Dose-dependent delivery of genes to the cerebral cortex via the nasal route.

The use of nucleic acids to treat various brain diseases could offer new therapeutic modalities, providing the nucleic acids may be effectively delivered to areas of the brain using non-toxic vectors. In this study, we present evidence that genes may be successfully delivered in a dose-dependent manner via the nose, primarily to the cerebral cortex using a 6-O-glycolchitosan (GC) formulation of plasmid DNA. Positively charged (zeta potential = +13 - + 25 mV) GC-DNA nanoparticles of 100-500 nm in diameter with favourable cell biocompatibility were shown to deliver the reporter Green Fluorescent Protein (GFP) plasmid to the U87MG cell line and the resulting protein expression was not significantly different from that obtained with Lipofectamine 2000.

Quaternary Ammonium Palmitoyl Glycol Chitosan (GCPQ) Loaded with Platinum-Based Anticancer Agents-A Novel Polymer Formulation for Anticancer Therapy.

Quaternary ammonium palmitoyl glycol chitosan (GCPQ) has already shown beneficial drug delivery properties and has been studied as a carrier for anticancer agents. Consequently, we synthesised cytotoxic platinum(IV) conjugates of cisplatin, carboplatin and oxaliplatin by coupling via amide bonds to five GCPQ polymers differing in their degree of palmitoylation and quaternisation. The conjugates were characterised by H and Pt NMR spectroscopy as well as inductively coupled plasma mass spectrometry (ICP-MS), the latter to determine the amount of platinum(IV) units per GCPQ polymer.

High-capacity glycol chitosan-based nanoemulsion for efficient delivery of disulfiram.

Disulfiram (DS) is an anti-alcoholism drug capable of acting against important and hard-to-treat cancers. The drug's relative instability and variable absorption/distribution have led to its variable pharmacokinetics and suboptimal exposure. Hence, it was hypothesised that a nano-enabled form of DS might be able to overcome such limitations.

Platinum(IV)-Loaded Degraded Glycol Chitosan as Efficient Platinum(IV) Drug Delivery Platform.

A new class of anticancer prodrugs was designed by combining the cytotoxicity of platinum(IV) complexes and the drug carrier properties of glycol chitosan polymers: Unsymmetrically carboxylated platinum(IV) analogues of cisplatin, carboplatin and oxaliplatin, namely (OC-6-44)-acetatodiammine(3-carboxypropanoato)dichloridoplatinum(IV), (OC-6-44)-acetaodiammine(3-carboxypropanoato)(cyclobutane-1,1-dicarboxylato)platinum(IV) and (OC-6-44)-acetato(3-carboxypropanoato)(1R,2R-cyclohexane-1,2-diamine)oxalatoplatinum(IV) were synthesised and conjugated via amide bonding to degraded glycol chitosan (dGC) polymers with different chain lengths (5, 10, 18 kDa). The 15 conjugates were investigated with H and Pt NMR spectroscopy, and average amounts of platinum(IV) units per dGC polymer molecule with ICP-MS, revealing a range of 1.3-22.

Quantification of Epicardial Adipose Tissue Volume and Attenuation for Cardiac CT Scans Using Deep Learning in a Single Multi-Task Framework.

Background: Recent studies have shown that epicardial adipose tissue (EAT) is an independent atrial fibrillation (AF) prognostic marker and has influence on the myocardial function. In computed tomography (CT), EAT volume (EATv) and density (EATd) are parameters that are often used to quantify EAT. While increased EATv has been found to correlate with the prevalence and the recurrence of AF after ablation therapy, higher EATd correlates with inflammation due to arrest of lipid maturation and with high risk of plaque presence and plaque progression.

Brain Gene Silencing with Cationic Amino-Capped Poly(ethylene glycol) Polyplexes.

Therapeutic gene silencing in the brain is usually achieved using highly invasive intracranial administration methods and/or comparatively toxic vectors. In this work, we use a relatively biocompatible vector: poly(ethylene glycol) star-shaped polymer capped with amine groups (4APPA) via the nose to brain route. 4APPA complexes anti- itchy E3 ubiquitin protein ligase (anti-ITCH) siRNA to form positively charged (zeta potential +15 ± 5 mV) 150 nm nanoparticles.

Ultrasmall-in-Nano: Why Size Matters.

Gold nanoparticles (AuNPs) are continuing to gain popularity in the field of nanotechnology. New methods are continuously being developed to tune the particles' physicochemical properties, resulting in control over their biological fate and applicability to in vivo diagnostics and therapy. This review focuses on the effects of varying particle size on optical properties, opsonization, cellular internalization, renal clearance, biodistribution, tumor accumulation, and toxicity.

Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes.

Gene delivery to the cerebral cortex is challenging due to the blood brain barrier and the labile and macromolecular nature of DNA. Here we report gene delivery to the cortex using a glycol chitosan-DNA polyplex (GCP). In vitro, GCPs carrying a reporter plasmid DNA showed approximately 60% of the transfection efficiency shown by Lipofectamine lipoplexes (LX) in the U87 glioma cell line.

Surface enhanced deep Raman detection of cancer tumour through 71 mm of heterogeneous tissue.

Detection of solid tumours through tissue- from depths relevant to humans- has been a significant challenge for biomedical Raman spectroscopy. The combined use of surface enhanced Raman scattering (SERS) imaging agents with deep Raman spectroscopy (DRS), i.e.

The topical ocular delivery of rapamycin to posterior eye tissues and the suppression of retinal inflammatory disease.

Treatment of posterior eye diseases with intravitreal injections of drugs, while effective, is invasive and associated with side effects such as retinal detachment and endophthalmitis. In this work, we have formulated a model compound, rapamycin (RAP), in nanoparticle-based eye drops and evaluated the delivery of RAP to the posterior eye tissues in a healthy rabbit. We have also studied the formulation in experimental autoimmune uveitis (EAU) mouse model with retinal inflammation.

Particulate levodopa nose-to-brain delivery targets dopamine to the brain with no plasma exposure.

Levodopa (L-DOPA) is an oral Parkinson's Disease drug that generates the active metabolite - dopamine (DA) in vivo. However, oral L-DOPA exhibits low oral bioavailability, limited brain uptake, peripheral DA-mediated side effects and its poor brain bioavailability can lead to long-term complications. Here we show that L-DOPA forms stable (for at least 5 months) 300 nm nanoparticles when encapsulated within N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ).

Amphotericin B Polymer Nanoparticles Show Efficacy against Species Biofilms.

Purpose: Chronic infections of are characterised by the embedding of budding and entwined filamentous fungal cells into biofilms. The biofilms are refractory to many drugs and biofilms are associated with ocular fungal infections. The objective was to test the activity of nanoparticulate amphotericin B (AmB) against biofilms.

A Cost Analysis of Cardiac Magnetic Resonance Imaging in the Diagnostic Pathway of Patients Presenting With Unexplained Acute Myocardial Injury and Culprit-Free Coronary Angiography.

To determine financial implications of implementing cardiac magnetic resonance imaging (CMR) in the diagnostic pathway of a population with unexplained acute myocardial injury and normal coronary angiography. We performed a focused cost-benefit analysis using a hypothetical population of 2,000 patients with unexplained acute myocardial injury and normal coronary angiography divided into two groups to receive either standard or CMR guided management over a 10-year period. As healthcare practice and costs considerably vary geographically and over time, an algorithm with 15 key variables was developed to permit user-defined calculations of cost-benefit and other analyses.

SARS-CoV-2 inhibition using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray.

There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19.

Development of Bio-Functionalized, Raman Responsive, and Potentially Excretable Gold Nanoclusters.

Gold nanoparticles (AuNPs) are used experimentally for non-invasive in vivo Raman monitoring because they show a strong absorbance in the phototherapeutic window (650-850 nm), a feature that is accompanied by a particle size in excess of 100 nm. However, these AuNPs cannot be used clinically because they are likely to persist in mammalian systems and resist excretion. In this work, clustered ultrasmall (sub-5 nm) AuNP constructs for in vivo Raman diagnostic monitoring, which are also suitable for mammalian excretion, were synthesized and characterized.

Polymeric Micelles for the Enhanced Deposition of Hydrophobic Drugs into Ocular Tissues, without Plasma Exposure.

Commercial topical ocular formulations for hydrophobic actives rely on the use of suspensions or oil in water emulsions and neither of these formulation modalities adequately promote drug penetration into ocular tissues. Using the ocular relevant hydrophobic drug, cyclosporine A (CsA), a non-irritant ocular penetration enhancer is showcased, which may be used for the formulation of hydrophobic actives. The activity of this penetration enhancer is demonstrated in a healthy rabbit model.

Tissue-Engineering the Fibrous Pancreatic Tumour Stroma Capsule in 3D Tumouroids to Demonstrate Paclitaxel Response.

Pancreatic cancer is a unique cancer in that up to 90% of its tumour mass is composed of a hypovascular and fibrotic stroma. This makes it extremely difficult for chemotherapies to be delivered into the core of the cancer mass. We tissue-engineered a biomimetic 3D pancreatic cancer ("tumouroid") model comprised of a central artificial cancer mass (ACM), containing MIA Paca-2 cells, surrounded by a fibrotic stromal compartment.

Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles.

Short dwell-time and poor penetration of the bladder permeability barrier (BPB) are the main obstacles to intravesical treatments for bladder diseases, and is evidenced by the lack of such therapeutic options on the market. Herein, we demonstrate that by finely tuning the molecular weight of our cationic polymer mucoadhesive nanoparticles, we enhanced our gene transfer, leading to improved adherence and penetrance through the BPB in a safe and efficient manner. Specifically, increasing the polymer molecular weight from 45 kDa to 83 kDa enhanced luciferase plasmid transfer to the healthy murine bladder, leading to 1.

A polymeric aqueous tacrolimus formulation for topical ocular delivery.

Tacrolimus (TAC) suspension is used to treat moderate to severe atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). The objectives of this study were to formulate the hydrophobic compound TAC (TAC) in an aqueous eye drop formulation and study its ocular biodistribution on topical ocular application to a healthy rabbit model, with the overall aim of using the formulation to treat AKC and VKC. A thin-film hydration method was used to encapsulate TAC within the chitosan-based amphiphile: N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (Molecular Envelope Technology - MET) in an aqueous formulation.

Down-regulation of GP130 signaling sensitizes bladder cancer to cisplatin by impairing Ku70 DNA repair signaling and promoting apoptosis.

Chemoresistance is one of the barriers for the development of bladder cancer treatments. Previously, we showed that glycoprotein-130 (GP130) is overexpressed in chemoresistant bladder cancer cells and that knocking down GP130 expression reduced cell viability. In our current work, we showed that down-regulation of GP130 sensitized bladder cancer cells to cisplatin-based chemotherapy by activating DNA repair signaling.

Nanoparticulate Mycophenolic Acid Eye Drops - Analytical Validation of a High Performance Liquid Chromatography Assay and Stability Studies.

Background: Mycophenolic acid (MPA), an immunosuppressive agent, is used orally to reduce corneal graft rejection. However, its oral use is associated with gastrointestinal side effects.

Objectives: This study aims to prepare: MPA nanoparticle eye drops and a validated analytical method.