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Results

FKBPL Gene Therapy for Age-Related Macular Degeneration 27 Apr 2017

This research project is designed to interrogate an alternative therapeutic for age-related macular degeneration. FKBPL is an anti-angiogenic protein that has a mechanism of action independent of the VEGF pathway. As such this project will deliver DNA than encodes the FKBPL protein in vitro and the molecular markers of angiogenesis will be measured. The novel peptide delivery sequence, termed RALA (WO2014087023) will be used to deliver the FKBPL DNA to the nucleus of the cells where the therapeutic protein can be made. Key Goals include: Characterisation of the RALA/FKBPL nanoparticles In vitro culture of human retinal pigment epithelial cells (ARPE-19), ACBR 183 primary human retinal pericyte cells, ACBR181 primary human retinal microvascular endothelial cells and choroidal endothelial cells (RF6A) Learning a range of molecular techniques including FACS analysis, rtPCR, IHC, western blot and migration/tubule formation assays Development of transferable skills such as health and safety knowledge in a laboratory, presentation skills, data analysis, experimental design, critical thinking and scientific report writing skills. It is anticpated that at the end of this placement that the student will have acquired an in depth knowledge of what a career in research entails and have learnt several techniques that can be employed post degree.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

(Pilot) Performance of EArly Retinal Laser (PEARL) 16 Nov 2015

The prevalence of diabetes in China has risen tenfold since 1981. Virtually all of China's 114 million diabetic persons willdevelop diabetic retinopathy (DR) eventually, and timely laser treatment reduces blindness by 50%. Still, only 10% of ruralpersons with DR in China receive treatment, partly because current care requires them to be followed for several yearsbefore reaching treatment criteria, during which many are lost.Our recent review suggests that earlier treatment, which could reduce the compliance burden, may be clinically efficaciousand cost effective, but current evidence is insufficient. Our pilot work confirms rural patients find long-term adherencedifficult, and earlier treatment is acceptable to patients and providers. We now propose a pilot randomised trial to determinewhether earlier laser treatment improves outcomes and compliance among those with diabetic retinopathy in China.Patients will be recruited from one of China's largest hospitals, and treated after training provided by the top-ranked eyehospital in the country. Participants with severe non-proliferative diabetic retinopathy (NPDR) in both eyes will berandomized to receive: pan-retinal photocoagulation (PRP) applied immediately in one eye at random and PRP in thefellow eye only when proliferative diabetic retinopathy (PDR) develops (Early Intervention-n=100) or PRP at the PDR stagein both eyes (Standard Care group-n=100). The latter group is needed in particular, to test whether early laser treatmenthas an effect on adherence.At 1 year follow-up, the primary outcome will be progression to PDR, with secondary outcomes including loss of vision,complications, quality of life and cost effectiveness. In addition to informing a full trial, this study will address questions of importance to diabetic eye care in low resourcesettings by validating physician clinical diagnosis of DR compared to more expensive technologies and testing a simplifieddefinition of severe NPDR.

Amount: £29,026
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration" (REALIST) 23 Nov 2015

Dr Cecilia O'Kane, Queen's University Belfast will lead a study to examine the safety and efficacy of a novel umbilical cord-derived, mesenchymal stromal cell (ORBCELC) in patients with moderate to severe ARDS, in a phase 112a rollover design. ARDS is a common condition in the ICU affecting more than 20% ventilated patients, or >20,000 patients per year in the UK. Up to 40% die. Survivors frequently suffer long term disability, both physically and psychologically. There is currently no pharmacological therapy that changes outcome from this condition. In the phase 1 study the maximum dose of ORBCEL-C cells that can be delivered in a single infusion to patients within 72 hours of onset of ARDS will be determined. This dose will then be used in a randomized, double blind placebo controlled phase 2a clinical trial, to test safety and efficacy of ORBCEL-C cells in patients with moderate to severe ARDS." A treatment that improved outcome from ARDS would therefore have huge impact on population health

Amount: £1,678,637
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Institutional Strategic Support Fund 07 Sep 2016

Not available

Amount: £360,000
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Hydrogel-forming microneedles for periodontal bio-sensing 31 May 2018

This project aims to demonstrate that a swellable-hydrogel system of tiny projections, arranged on a thin baseplate can be used to imbibe periodontal crevicular fluid as a method of minimally invasive fluid collection. We aim to select and optimise the most appropriate microneedle design and formulation for fluid sampling from the gingival sulcus. This will involve formulation of aqueous blends of biocompatible polymers, cross-linked to form a hydrogel matrix that is hard in the dry state. This devices could be inserted between the teeth and gum margins, into the gingival sulcus where the hydrogel can swell and uptake periodontal crevicular fluid. Removing the device intact, it can be placed into an elution buffer. Pro-inflammatory biomarkers such as IL 1, IL 2 or IL 6 that have adhered to the hydrogel surface, or imbibed into the matrix can be washed off and assayed using commercially available ELISA kits. To achieve these aims, hydrogel swelling capacity and mechanical strength will be assessed using swelling studies and texture analysis for fracture force characterisation. Thin films of formulations will be cast, dried, cross-linked and assessed for cross-link density using FTIR. Commercially available ELISAs will be used to detect pro-inflammatory markers from pre-defined calibrator fluids.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

3D printable antimicrobial materials for the development of safer medical devices 31 May 2018

Nosocomial infections primarily result from bacterial attachment to surfaces and biofilm formation, for example of implanted medical devices. Such infections demonstrate significant resistance to antibacterial treatment, resulting in extended hospital stays, increased healthcare costs, patient morbidity and potential mortality. The incorporation of antibiotics into the surface of a medical device could prevent bacterial colonization but it contributes to the antibiotic resistance problem. A good approach to prevent this is to prepare medical devices with inherent antimicrobial properties. In the present work, we propose development of 3D printable materials containing an antimicrobial biomolecule obtained from renewable sources, lignin. For this purpose, lignin will be combined with two different 3D printable materials: poly(lactic acid) (PLA), to create solid coatings, and poly(vinyl alcohol) (PVA), to create hydrogel coatings. The present project combines the versatility of 3D printing for the preparation of medical materials with the antimicrobial properties of lignin with the aim of creating safer, greener and cheaper medical materials. The main goals of the project are: Preparation of PLA-lignin and PVA-lignin hybrid materials for 3D printing Characterization of the resulting 3D printed materials Evaluation of the antimicrobial properties of the resulting 3D printed materials

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Small molecule inhibitors of the anti-apoptotic FLIP-FADD protein-protein interaction for the treatment of non-small cell lung cancer 01 Oct 2017

In most organs and tissues, old cells are constantly dying and being replaced by new cells. This balance is critical for normal organ/tissue function and is maintained by a balance between new cells being created by cell division and old cells dying by a process known as "apoptosis". One of the key characteristics of cancers is that the old cells do not die efficiently by apoptosis and therefore accumulate giving rise to a tumour that ultimately disrupts organ function. This block in apoptosis is also a major problem when it comes to treating cancers as the effectiveness of chemotherapies and radiotherapies usually rely on their ability to activate this type of cell death. Dr Daniel Longley's team at Queen's University of Belfast have identified an intra-cellular protein called "FLIP" that plays a critical role in preventing the death of cancer cells treated with chemotherapy and radiotherapy. This protein plays a prominent role in increasing the resistance to therapy in a number of types of cancer, including non-small cell lung cancer, which is a particularly drug-resistant cancer and is the focus of this proposal. The project team plan to generate drugs to block FLIP's function and thereby overcome drug resistance and improve the therapeutic management of patients with this disease.

Amount: £1,571,668
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Open Access Award 2017/18 30 Sep 2018

Not available

Amount: £25,061
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Oxytocin delivery using a microarray patch for postpartum haemorrhage 31 May 2018

This project involves development of a novel microarray patch (MAP) device for the delivery of oxytocin to prevent and treat post-partum haemorrhage (PPH). Oxytocin is recommended by the World Health Organisation as the gold-standard treatment for PPH but is often not available in low income countries as it requires cold storage and a trained health professional to administer the injection. Polymeric MAPs are minimally invasive devices, consisting of an array of micro projections, up to 600 µm in length. On application they painlessly penetrate the outermost layer of the skin, the stratum corneum and imbibe interstitial skin fluid. This causes the matrix to swell and creates a continuous network through which oxytocin would reach the systemic circulation. Oxytocin would be formulated in to a drug reservoir that is separate from the MAP, such as a lyophilised tablet, which could increase its stability. Several key parameters need to be tested: 1. Ability to load adequate oxytocin levels in to a drug reservoir. 2. Ability of an adequate concentration of oxytocin to permeate the skin with a MAP and the time taken to reach therapeutic levels. 3. Stability of oxytocin in the drug reservoir at 40oC and 75% relative humidity.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Sustained release of drug-loaded nanoparticles from a novel vaginal ring design 31 May 2018

Sustained-release drug products are useful in prolonging the action of a drug in the body by maintaining therapeutic concentrations of the drug over extended time periods. Here, we are particularly interested in polymeric vaginal rings for long-acting vaginal administration of drugs (1). Various steroid-releasing vaginal ring products are currently marketed for hormonal contraception and estrogen replacement therapy, and a new ring device – developed in part by the Queen's University Belfast (QUB) and offering sustained release of the antiretroviral drug dapivirine for HIV prevention – is due to reach market soon. However, a major limitation of current vaginal ring technologies is that they are generally not useful for administration of either large molecule drugs or drug-loaded nanoparticles, due to limited solubility and/or diffusion in the polymeric materials used to manufacture rings. Here, we propose for the first time to test a novel vaginal ring developed at QUB for sustained release of drug-loaded nanoparticles, with potential applications in prevention/treatment of sexually transmitted infections, mucosal immunisation, and treatment of cervicovaginal cancers. The ring device comprises orifices in the ring surface which expose the underlying drug-loaded core. The ring is easy to manufacture using highly-scalable and conventional injection molding technologies.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Microneedle delivery of the anti-psychotic medicine haloperidol decanoate 31 May 2018

This project involves development of a novel dissolving microneedle array device, incorporating a nano suspension of haloperidol decanoate to provide transdermal delivery of a formulation that will dissolve in skin and act as a depot. Dissolving microneedle arrays are minimally invasive devices, consisting of an array of micro projections arranged on a baseplate in a defined configuration. These microneedles, up to 600 µm in length, are hard in the dry state and when applied to the skin using manual thumb pressure, painlessly penetrate the outermost layer of the skin, the stratum corneum. The needle tips dissolve in interstitial fluid releasing the nano suspension formulation into the viable skin tissue. Haloperidol can then be slowly and constantly be release over long periods of time to maintain constant plasma levels. A number of key parameters need to be assessed: 1. Nanosuspension formulation using a nano precipitate/ultra sonification method 2. Nanosuspension physicochemical characterisation for particle size and zeta potential 3. Formulation of microneedle arrays using aqueous blends of biocompatible polymers 4. In skin dissolution of the microneedle formulations

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Microneedles: Bypassing the Gastrointestinal Microbiota to Circumvent Antibiotic Resistance 11 Jul 2017

We will validate a novel antibiotic delivery strategy which overcomes development of resistance, thus extending the lifespan of existing antibiotics. It will reduce deleterious effects on indigenous microbiomes by minimising exposure of the gut microbiome (a major reservoir of antimicrobial resistance). Importantly, it will also permit at-home delivery of new antibiotics that would otherwise require in-patient administration. Our key questions are: Q1 How do we optimise novel microneedle systems for transdermal delivery of clinically-effective antibiotic doses? Q2 Does microneedle delivery prevent exposure of the gut microbiome to antibiotics and avoid disruption of this community? Q3 Does microneedle delivery reduce/prevent emergence of resistance in key opportunistic pathogens which are normal residents of the human gut microbiome? Q4 Does microneedle delivery avoid selection of resistant strains from outside the gut microbiome and their incorporation into the gut microbiome? Q5 Can microneedle delivery treat infection as successfully as conventional orally- or intravenously-administered antibiotics? We will: Formulate microneedle systems containing model antibiotics Illustrate in vitro and in vivo transdermal delivery Demonstrate avoidance of gut microbiome exposure and resistance-sparing capabilities in vivo relative to oral delivery Show efficacy of transdermally-delivered antibiotics against microbial infections in vivo

Amount: £908,272
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

3D bioprinting for enhanced biosensing, regenerative medicine and pharmaceutical manufacture 06 Jul 2017

The GeSiM BioScaffolder 3.1 printer is a flexible 3D bio-printer with a unique piezoelectric micro-pipetting system for pico- and nano-litre spotting of cells and biomolecules, as well as pneumatically-actuated cartridges for precise printing of highly viscous materials (e.g. molten polymers) on definable coordinates within a scaffold structure or on flat surfaces. This combination of both technologies is unique and not available on competitor 3D printers. The BioScaffolder can print polymers at temperatures up to 250°C, while cells and biomolecules (e.g. enzymes, proteins) can be maintained at 37°C. This innovative approach allows struts of mechanically-stiff materials to be combined with cell-friendly materials (e.g. hydrogels) containing suspended cells in novel regenerative medicine approaches. The instrument automatically aligns print tools of different dimensions by means of a 3-axis light barrier. Struts of up to three different materials can be combined, even in a single layer. Individual cells, cell suspensions and aqueous polymer solutions can be printed onto substrates for applications in single-cell analyses, biosensing and drug delivery. Importantly, the Bioscaffolder can be interfaced with existing analytical equipment, with individual cells or solutions printed directly into instrument sample holders, or onto microfluidic chips or biosensor substrates.

Amount: £155,000
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Novel Peptoid Hydrogels as Long Acting Injectable Drug Delivery Systems 12 May 2017

Long-acting injectable (LAI) nanosuspensions comprising water-insoluble drugs are already widely marketed for treatment of schizophrenia and are presently being evaluated in late-stage clinical studies as formulation strategies for pre-exposure prophylaxis (PrEP) against HIV infection. Alternative formulations are needed to overcome some of the inherent disadvantages with nanosuspension injections, including the requirement for use of water-insoluble actives, the formation of amorphous drug during milling, and difficulties around manufacturing scale-up. This project will investigate for the first time the use of enzyme-responsive peptoid hydrogelators as a new technology platform for development of LAI medicines. Peptoids are biocompatible molecules that mimic naturally occurring peptides. They form structured, tissue-like, hydrogel networks in aqueous environments and can offer sustained release of drugs. Here, we aim to investigate the potential of novel peptoid hydrogels for long–acting subcutaneous drug administration. The formulations will comprise a peptoid backbone capable of hydrogelation; a phosphate group to increase aqueous solubility and whose enzymatic removal triggers hydrogel formation in vivo; and a model antiretroviral molecule attached via a physiologically hydrolysable group. The goals include: (i) characterisation of antiretroviral-conjugated peptoids for their ability to form hydrogels; (ii) testing the biocompatibility of peptoid hydrogels; and (iii) evaluation of sustained drug release properties.

Amount: £99,981
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Small molecule inhibitors of the anti-apoptotic FLIP-FADD protein-protein interaction for the treatment of non-small cell lung cancer 02 Oct 2016

In most organs and tissues, old cells are constantly dying and being replaced by new cells. This balance is critical for normal organ/tissue function and is maintained by a balance between new cells being created by cell division and old cells dying by a process known as "apoptosis". One of the key characteristics of cancers is that the old cells do not die efficiently by apoptosis and therefore accumulate giving rise to a tumour that ultimately disrupts organ function. This block in apoptosis is also a major problem when it comes to treating cancers as the effectiveness of chemotherapies and radiotherapies usually rely on their ability to activate this type of cell death. Dr Daniel longley's team at Queen's University of Belfast have identified an intra-cellular protein called "FLIP" that plays a critical role in preventing the death of cancer cells treated with chemotherapy and radiotherapy. This protein plays a prominent role in increasing the resistance to therapy in a number of types of cancer, including non-small cell lung cancer, which is a particularly drug-resistant cancer and is the focus of this proposal. The project team plan to generate drugs to block FLIP's function and thereby overcome drug resistance and improve the therapeutic management of patients with this disease.

Amount: £209,451
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Vacation Scholarships 2017 - Queen's University Belfast 16 Jun 2017

Vacation Scholarships 2017 - Queen's University Belfast

Amount: £15,500
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Ocular Drug Delivery by Using Preformed Biodegradable Implants 27 Apr 2017

Glaucoma can result in damage to the optic nerve and vision loss, which is a leading cause of blindness. Eye drops is the most commonly used treatment for glaucoma in clinic. This treatment is associated with low bioavailability of the applied drug and unpleasant side effects resulted from frequent administrations. This study aims to develop novel ocular drug delivery systems using drug-loaded biodegradable implants for the treatment of glaucoma. In this study, drug-loaded implants composed of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) will be formulated. The structure, thermal properties, mechanical properties, degradation behaviors and in vitro drug release profiles of the implants will be further investigated. These drug-loaded implants can provide a sustained release of the incorporated drug, reduce the burden of frequent administration and finally improve patient compliance.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Ocular Drug Delivery by Using Phase Invertible Implants 27 Apr 2017

Age–related macular degeneration (AMD) currently affects more than 600,000 people in the UK and is the leading cause of vision loss. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) is an effective treatment for AMD patients. However, frequent injections are required in the treatment, which is expensive and often associated with complications and poor patient tolerance. This study focuses on the development of novel ocular drug delivery using in situ forming implants to treat AMD. In this study, in situ formed implants composed of biodegradable polymers will be formulated using PLGA and biocompatible organic solvent. Various properties of the in situ forming systems will be investigated, such as thermal properties, rheological properties, degradation behaviors and in vitro drug release profiles. These in situ forming implants can sustain the release of incorporated drugs, reduce complications caused by frequent administration and ultimately improve patient comfort.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast

Immunomodulatory effect of cigarette- and electronic cigarette- exposed respiratory pathogens on macrophages in vitro 27 Apr 2017

It has been established that cigarette smoke and E-cigarette vapour can activate inflammatory response and impair antimicrobial functions of human immune cells. However, the direct effects of cigarette smoke and E-cig vapour on respiratory pathogens is less well known. The aim of this project is to further explore the effect of cigarette smoke extract (CSE) and e-cigarette smoke extract (ECSE) on important human respiratory pathogens and their interaction with the host. The immunomodulatory effects of CSE/ECSE exposed respiratory pathogens have on macrophages in vitro will be determined. Western blot analysis will be used to detect activation of the canonical NF-kappaB pathway and caspase-1 activation whilst ELISA assays will be utilized to measure the expression of the cytokines IL-8, IL-12, TNF-alpha and IL-1beta. In addition, susceptibility of bacteria to macrophage phagocytosis and killing will be measured. The findings of this project will provide valuable information about the direct effect of cigarette smoke and e-cigarette on the lung microbiome and its interaction with host immune cells.

Amount: £0
Funder: The Wellcome Trust
Recipient: Queen's University Belfast