Formulation and Drug Delivery Research
The projects outlined below are indicative of those undertaken by researchers under the supervision of staff within the Formulation and Drug Delivery group. These are examples of projects currently available for students with their own source of funding. The School of Pharmacy and Biomolecular Sciences does not offer any scholarships or funding to International students. Any studentships that do become available will be advertised on the main LJMU vacancies website. Note that projects similar in nature to those already being undertaken by current and past postgraduate students are also usually available and can be accessed via the research members page.
For further information on any of these projects or the postgraduate application process please contact Dr Gillian Hutcheon
Metal-ion exchanged antimicrobial clays for wound care
For centuries clays have been used for healthcare purposes, usually by topical application (as dermatological protectors and cosmetics) or oral formulations as stomach remedies (laxatives, antidiarrhetics and gastrointestinal protectors). The antibacterial properties of heavy metals are well documented and their use to prevent infection in wounds is not novel (Flamazine and Actisorb® Silver 220 products). The limiting factor is the large concentration of metal ions required to achieve sufficient contact with the bacterial cells, and their reactivity with anions (mainly Cl-) in aqueous environments, resulting in reduced antimicrobial effects. The concept of antimicrobial metal-ion exchanged clay minerals could afford a simple and economical approach to the problem of maintaining a sterile environment of a healing wound.
The combination of a hydrating gel-forming material able to provide sustained control of bacterial ingression would likely be of great benefit in healthcare applications, such as wound management. This is a highly multidisciplinary project involving various aspects of chemistry, pharmaceutics, microbiology and clinical management. The collaboration between Rockwood Additives Ltd. (the leading producer and supplier of clay based products), lab-based researchers at LJMU and NHS clinical advisors within the Tissue Viability Department at the Royal Liverpool and Broadgreen University Hospitals, will enable a quicker progress towards a clinically usable product.
Biodegradable polymers for drug delivery: Design and synthesis and evaluation
These projects focuses on the enzyme catalysed synthesis of novel, functionalised biodegradable polymers for drug delivery. This includes the design, synthesis and modification of functionalised biodegradable polymers for micro- and nanoparticle drug and/or protein delivery. Polymers are characterised using NMR, IR, GPC, HPLC, thermal analysis etc. Drugs or other chemical moieties can be attached to backbone functional groups to improve drug encapsulation or release profiles. The project will continue studies on the application of functional polyester particles for the delivery of drugs and/or biomacromolecules for the treatment of diseases such as cystic fibrosis and cancer. Investigations into the cell toxicity of the polymers and studies into the development a cell culture based assay to monitor the release of drugs from the polymer based particles will provide results for the potential of these colloidal systems to successfully deliver active compounds to the site of action.
Towards the delivery of stable proteins
The delivery of proteins via the respiratory tract has great potential to treat a range disease states. However, maintaining an active protein conformation during the formulation and delivery process can be challenging. This particular project focuses on the stabilisation of proteins for delivery using biodegradable polymeric microparticles. This novel research will explore methods of retaining protein and enzyme activity during encapsulation in microparticles prepared from novel polymers. This will be achieved by exploring a variety of methods of stabilising proteins during formulation including the encapsulation of stable protein coated micro crystals (PCMC) in polymeric particles. Crystal forms of proteins will be produced and assessed in terms of stability and activity pre-and post formulation. Langmuir monolayers will be used to attempt to crystallise the material and AFM used to probe the resulting crystal structure. In vitro aerosol performance of protein containing particles will be formulated as dry powders and analysed using cascade impaction studies.
Gene delivery for the treatment of cancers
Cancer is a leading cause of death worldwide and patients are treated by surgery, radiotherapy and chemotherapy. The latter two therapies are non-specific and patients suffer from side-effects due to destruction of healthy tissues. Molecular approaches using gene therapy targeting the death of cancer cells appears to be an attractive therapy option. This project will investigate the encapsulation of genetic material within novel polymer-based nanoparticle delivery systems incorporating ligands to actively target cancer cells. This will be achieved using a combination of disciplines including polymer chemistry, drug delivery and formulations together with molecular and cell biology. Investigations will include design, synthesis and evaluation of novel polymers for gene delivery to release their cargo at specific pH, with minimum toxicity and optimised cell uptake.
Mucinolytic enzymes as potential treatments for pulmonary Cystic Fibrosis
Prognosis and treatment of cystic fibrosis (CF) has improved significantly over the past few decades, increasing the life expectancy of patients. Currently available treatments are aimed at alleviating the symptoms and correcting the protein dysfunction. However, the main issue is still the delivery of therapeutics. Some enzymes have the ability to degrade mucins, the glycoproteins found in mucus, and thus may have a potential use in clearing the viscous mucous secretions in the lungs of CF patients. Projects within this study include screening for mucinolytic enzyme producing microorganisms and characterising their produced enzymes and assessing the feasibility of incorporating these enzymes into suitable delivery systems.
Pulmonary aerosol drug delivery systems
This includes studying the shape of the upper airway during inhalation via the devices by using magnetic resonance imaging, applying computational fluid dynamics to study the particle flow in the upper airway, optimising the shape of the upper airway and characteristics of the aerosol devices to maximise drug lung deposition, formulation of dry powder inhalers.
Crystallisation in Emulsions
The use of surfactants as crystallisation additives is well known and can be used to engineer crystalline products in terms of polymorph and morphology. Crystallisation in emulsions can have the additional affect of limiting the solution volume or allowing the slow diffusion of solvents and additives via the continuous phase. Aims are to exert a high degree of control over the final product in terms of polymorph, size and morphology.
Compression of re-crystallised pharmaceutical materials
The physicochemical properties of active pharmaceutical ingredients and excipients can be manipulated by re-crystallisation or co-crystallisation techniques. The aim is to investigate the effects of crystallisation conditions on the particle characteristics of actives and/or excipients and their subsequent compression properties.
Pharmaceutical Co crystal Screening
Pharmaceutical co crystals are rapidly emerging as a vehicle to increase solid form diversity and overcome poor pharmaceutical properties of API materials. Co crystals, are multi-component crystalline solids in which two different molecules (API and a co crystal former) are incorporated into a single solid phase. The development of novel methods for production and screening of co crystals would be investigated, with the use of molecular modelling to design co crystal pairings.
Development of novel oral dosage forms for paediatric drug delivery
Traditional oral delivery systems such as tablets and capsules are not suitable for children and whilst adult dosage forms can be manipulated to obtain suitably reduced doses for paediatric patients, inaccuracies often result from this practice. The aim is to investigate the potential for developing novel oral dosage forms such as orally disintegrating tablets (ODT's) and/or fast-dissolving films which can avoid swallowing difficulties and improve the accuracy of paediatric drug delivery.
Dissolution of drugs in biorelevant media
Dissolution of drugs is a prerequisite for absorption and bioavailability. In the gastrointestinal tract drugs are exposed to partially digested food. Despite this compendial media are simple solutions. This project will investigate the effect of food components on the dissolution behaviours of a selection of drugs indicating the effect of ingested meals on drug dissolution and bioavailability.
Engineering of pharmaceutically relevant crystals
Recently, the delivery of therapeutic agents via the respiratory tract has attracted significant attention as it offers a means by which to treat a wide range of local (i.e. asthma) and systemic (i.e. diabetes) disease states. Current research focuses on the development of advanced inhaled formulations (i.e. nano-sized respirable particles) for disease management. However, limited consideration has been given to how the crystal form and surface chemistry of an inhaled drug particle may influence the nature / extent of association with internal surfaces of the lung. Clearly, it would be of benefit to engineer material to maximise the physical interaction with pulmonary fluid. Here, we aim to rationally generate pharmaceutically relevant crystals in direct contact with simulated pulmonary surfactant monolayers and subsequently characterise the material via a range of pharmaceutical techniques. It is envisaged that when compared to commercially available preparations, the association between the engineered material (i.e. that demonstrating complementarity with pulmonary surfactant) and lung fluid will be enhanced, thus leading to improved formulations for inhaled therapy. The study may also provide a unique insight into the crystallisation propensity of active pharmaceutical ingredients once delivered to the respiratory system.